1743:
1003:, as this disease is likely to recur in the transplanted kidney if a calcineurin-inhibitor is used. However, on 7 October 2008, the FDA approved safety labeling revisions for sirolimus to warn of the risk for decreased renal function associated with its use. In 2009, the FDA notified healthcare professionals that a clinical trial conducted by Wyeth showed an increased mortality in stable liver transplant patients after switching from a calcineurin inhibitor-based immunosuppressive regimen to sirolimus. A 2019 cohort study of nearly 10,000 lung transplant recipients in the US demonstrated significantly improved long-term survival using sirolimus + tacrolimus instead of mycophenolate mofetil + tacrolimus for immunosuppressive therapy starting at one year after transplant.
676:
653:
1963:
40:
1782:
1795:
1137:
malformations in recent years, sirolimus has emerged as a new medical treatment option for both vascular tumors and vascular malformations, as a mammalian target of rapamycin (mTOR), capable of integrating signals from the PI3K/AKT pathway to coordinate proper cell growth and proliferation. Hence, sirolimus is ideal for "proliferative" vascular tumors through the control of tissue overgrowth disorders caused by inappropriate activation of the PI3K/AKT/mTOR pathway as an antiproliferative agent.
742:
1763:
1658:
2093:, increased elderly patients' immune response on an intermittent dose. This led to many in the anti-aging community self-experimenting with the compound. However, because of the different biochemical properties of Sirolimus the dosing is potentially very different than everolimus. Ultimately, due to known side effects of sirolimus, as well as inadequate evidence for optimal dosing, more research is required before sirolimus could be widely prescribed for this purpose.
31:
1154:
after using the drug. The reports involved a total of 84 patients, and improvement was observed in 94% of subjects, especially if treatment began during the early stages of the disease. Sirolimus treatment was applied in several different formulations (ointment, gel, solution, and cream), ranging from 0.003 to 1% concentrations. Reported adverse effects included one case of perioral dermatitis, one case of cephalea, and four cases of irritation.
2216:. In this application, rapamycin is added to cells expressing two fusion constructs, one of which contains the rapamycin-binding FRB domain from mTOR and the other of which contains an FKBP domain. Each fusion protein also contains additional domains that are brought into proximity when rapamycin induces binding of FRB and FKBP. In this way, rapamycin can be used to control and study protein localization and interactions.
9930:
794:
InChI=1S/C51H79NO13/c1-30-16-12-11-13-17-31(2)42(61-8)28-38-21-19-36(7)51(60,65-38)48(57)49(58)52-23-15-14-18-39(52)50(59)64-43(33(4)26-37-20-22-40(53)44(27-37)62-9)29-41(54)32(3)25-35(6)46(56)47(63-10)45(55)34(5)24-30/h11-13,16-17,25,30,32-34,36-40,42-44,46-47,53,56,60H,14-15,18-24,26-29H2,1-10H3/b13-11+,16-12+,31-17+,35-25+/t30-,32-,33-,34-,36-,37+,38+,39+,40-,42+,43+,44-,46-,47+,51-/m1/s1
1641:
right dose for their condition. This is determined by taking a blood sample before the next dose, which gives the trough level. However, good correlation is noted between trough concentration levels and drug exposure, known as area under the concentration-time curve, for both sirolimus (SRL) and tacrolimus (TAC) (SRL: r2 = 0.83; TAC: r2 = 0.82), so only one level need be taken to know its
2188:, or cystic hygroma, is an abnormal growth of lymphatic vessels that usually affects children around the head and neck. Treatment often consists of to removal of the tissue, but the rate of recurrence is high. Sirolimus has shown evidence of being helpful in alleviating symptoms and reducing the size of the malformation.
2084:
of various diseases of aging. Sirolimus was first shown to extend lifespan in wild-type mice in a study published by NIH investigators in 2009; the studies have been replicated in mice of many different genetic backgrounds. A study published in 2020 found late-life sirolimus dosing schedules enhanced
1153:
complex (TSC). Facial angiofibromas occur in 80% of patients with TSC, and the condition is very disfiguring. A retrospective review of
English-language medical publications reporting on topical sirolimus treatment of facial angiofibromas found sixteen separate studies with positive patient outcomes
2085:
mouse lifespan in a sex-specific manner where limited rapamycin exposure enhanced male lifespan but not female, providing evidence for sex differences in sirolimus response. The results are further supported by the finding that genetically modified mice with impaired mTORC1 signalling live longer.
1941:
it, thereby introducing the diversity of functionalities observed in rapamycin (figure 1). Once the linear polyketide is complete, L-pipecolic acid, which is synthesized by a lysine cycloamidase from an L-lysine, is added to the terminal end of the polyketide by an NRPS. Then, the NSPS cyclizes the
1727:
of rapamycin are organized into three multienzymes, RapA, RapB, and RapC, which contain a total of 14 modules (figure 1). The three multienzymes are organized such that the first four modules of polyketide chain elongation are in RapA, the following six modules for continued elongation are in RapB,
1022:
are possible side effects of sirolimus; therefore, some transplant centers prefer not to use it immediately after the transplant operation, but instead administer it only after a period of weeks or months. Its optimal role in immunosuppression has not yet been determined, and it remains the subject
1115:
to prevent restenosis in coronary arteries following balloon angioplasty. The sirolimus is formulated in a polymer coating that affords controlled release through the healing period following coronary intervention. Several large clinical studies have demonstrated lower restenosis rates in patients
1640:
The bioavailabiliy of sirolimus is low, and the absorption of sirolimus into the blood stream from the intestine varies widely between patients, with some patients having up to eight times more exposure than others for the same dose. Drug levels are, therefore, taken to make sure patients get the
1595:
mTOR has also been called FRAP (FKBP-rapamycin-associated protein), RAFT (rapamycin and FKBP target), RAPT1, or SEP. The earlier names FRAP and RAFT were coined to reflect the fact that sirolimus must bind FKBP12 first, and only the FKBP12-sirolimus complex can bind mTOR. However, mTOR is now the
1806:, prerapamycin (figure 2), is then modified (figure 3) by an additional five enzymes, which lead to the final product, rapamycin. First, the core macrocycle is modified by RapI, SAM-dependent O-methyltransferase (MTase), which O-methylates at C39. Next, a carbonyl is installed at C9 by RapJ, a
1978:
The antiproliferative effects of sirolimus may have a role in treating cancer. When dosed appropriately, sirolimus can enhance the immune response to tumor targeting or otherwise promote tumor regression in clinical trials. Sirolimus seems to lower the cancer risk in some transplant patients.
1205:
The most common adverse reactions (≥20% occurrence, leading to an 11% treatment discontinuation rate) observed with sirolimus in clinical studies for the treatment of lymphangioleiomyomatosis are: peripheral edema, hypercholesterolemia, abdominal pain, headache, nausea, diarrhea, chest pain,
1136:
Sirolimus is used to treat vascular malformations. Treatment with sirolimus can decrease pain and the fullness of vascular malformations, improve coagulation levels, and slow the growth of abnormal lymphatic vessels. Sirolimus is a relatively new medical therapy for the treatment of vascular
2061:(TSC), a congenital disorder that predisposes those afflicted to benign tumor growth in the brain, heart, kidneys, skin, and other organs. After several studies conclusively linked mTOR inhibitors to remission in TSC tumors, specifically subependymal giant-cell astrocytomas in children and
1427:, which results in diabetes-like symptoms. This includes decreased glucose tolerance and insensitivity to insulin. Sirolimus treatment may additionally increase the risk of type 2 diabetes. In mouse studies, these symptoms can be avoided through the use of alternate dosing regimens or
1908:
have been identified to code for enzymes that have a positive regulatory role in the preparation of rapamycin through the control of rapamycin PKS gene expression. Biosynthesis of this 31-membered macrocycle begins as the loading domain is primed with the starter unit,
2204:. While contrasted results were obtained in clinical trials, pre-clinical studies have shown that Rapamycin can mitigate GVHD by increasing the proliferation of regulatory T cells, inhibiting cytotoxic T cells and lowering the differentiation of effector T cells.
4461:
Aparicio JF, Molnár I, Schwecke T, König A, Haydock SF, Khaw LE, et al. (February 1996). "Organization of the biosynthetic gene cluster for rapamycin in
Streptomyces hygroscopicus: analysis of the enzymatic domains in the modular polyketide synthase".
4320:
Gregory MA, Gaisser S, Lill RE, Hong H, Sheridan RM, Wilkinson B, et al. (May 2004). "Isolation and characterization of pre-rapamycin, the first macrocyclic intermediate in the biosynthesis of the immunosuppressant rapamycin by S. hygroscopicus".
2088:
Sirolimus has potential for widespread use as a longevity-promoting drug, with evidence pointing to its ability to prevent age-associated decline of cognitive and physical health. In 2014, researchers at
Novartis showed a related compound,
2120:
When applied as a topical preparation, researchers showed that rapamycin can regenerate collagen and reverse clinical signs of aging in elderly patients. The concentrations are far lower than those used to treat angiofibromas.
1165:
The most common adverse reactions (≥30% occurrence, leading to a 5% treatment discontinuation rate) observed with sirolimus in clinical studies of organ rejection prophylaxis in individuals with kidney transplants include:
3999:
Errasti P, Izquierdo D, Martín P, Errasti M, Slon F, Romero A, et al. (October 2010). "Pneumonitis associated with mammalian target of rapamycin inhibitors in renal transplant recipients: a single-center experience".
1810:
monooxygenases (P-450). Then, RapM, another MTase, O-methylates at C16. Finally, RapN, another P-450, installs a hydroxyl at C27 immediately followed by O-methylation by Rap Q, a distinct MTase, at C27 to yield rapamycin.
5818:
4212:
McAlister VC, Mahalati K, Peltekian KM, Fraser A, MacDonald AS (June 2002). "A clinical pharmacokinetic study of tacrolimus and sirolimus combination immunosuppression comparing simultaneous to separated administration".
964:
In the EU, sirolimus, as
Rapamune, is indicated for the prophylaxis of organ rejection in adults at low to moderate immunological risk receiving a renal transplant and, as Hyftor, is indicated for the treatment of facial
1742:
3289:
Balestri R, Neri I, Patrizi A, Angileri L, Ricci L, Magnano M (January 2015). "Analysis of current data on the use of topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis complex".
1749:
1645:(PK) profile. PK profiles of SRL and of TAC are unaltered by simultaneous administration. Dose-corrected drug exposure of TAC correlates with SRL (r2 = 0.8), so patients have similar bioavailability of both.
2080:, specifically mTORC1, was first shown to be important in aging in 2003, in a study on worms; sirolimus was shown to inhibit and slow aging in worms, yeast, and flies, and then to improve the condition of
1066:
group in 89 patients for 12 months. The patients were observed for 12 months after the treatment had ended. The most commonly reported side effects of sirolimus treatment of LAM were mouth and lip ulcers,
2112:
are decreased, which suggests an immunosuppressive response. The duration of the inhibition and the exact extent to which mTORC1 and mTORC2 are inhibited play a role, but are not yet well understood.
1035:(LAM), a rare, progressive lung disease that primarily affects women of childbearing age. This made sirolimus the first drug approved to treat this disease. LAM involves lung tissue infiltration with
3765:
Das BB, Shoemaker L, Subramanian S, Johnsrude C, Recto M, Austin EH (March 2007). "Acute sirolimus pulmonary toxicity in an infant heart transplant recipient: case report and literature review".
2884:
4703:
Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, et al. (August 2005). "Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition".
3800:
Delgado JF, Torres J, José Ruiz-Cano M, Sánchez V, Escribano P, Borruel S, et al. (September 2006). "Sirolimus-associated interstitial pneumonitis in 3 heart transplant recipients".
1625:. It has linear pharmacokinetics. In studies on N=6 and N=36 subjects, peak concentration was obtained in 1.3 hours +/r- 0.5 hours and the terminal elimination was slow, with a
3341:
2877:"Aadi Bioscience Announces FDA Approval of its First Product Fyarro for Patients with Locally Advanced Unresectable or Metastatic Malignant Perivascular Epithelioid Cell Tumor (PEComa)"
2069:(Novartis's RAD001) to TSC patients off-label. Numerous clinical trials using both rapamycin analogs, involving both children and adults with TSC, are underway in the United States.
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9864:
5658:"Rapamycin inhibits the generation of graft-versus-host disease- and graft-versus-leukemia-causing T cells by interfering with the production of Th1 or Th1 cytotoxic cytokines"
5866:
1736:
is modified by the NRPS, RapP, which attaches L-pipecolate to the terminal end of the polyketide, and then cyclizes the molecule, yielding the unbound product, prerapamycin.
5107:
1561:, but it has a similar suppressive effect on the immune system. Sirolimus inhibits IL-2 and other cytokine receptor-dependent signal transduction mechanisms, via action on
7488:
2391:
2361:
2324:
4177:
Leung LY, Lim HK, Abell MW, Zimmerman JJ (February 2006). "Pharmacokinetics and metabolic disposition of sirolimus in healthy male volunteers after a single oral dose".
1602:
that identified FKBP12, Tor1, and Tor2 as the targets of sirolimus and provided robust support that the FKBP12-sirolimus complex binds to and inhibits Tor1 and Tor2.
9140:
9130:
4787:
Wendel HG, De
Stanchina E, Fridman JS, Malina A, Ray S, Kogan S, et al. (March 2004). "Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy".
5129:
Mannick JB, Del
Giudice G, Lattanzi M, Valiante NM, Praestgaard J, Huang B, et al. (December 2014). "mTOR inhibition improves immune function in the elderly".
3835:
McWilliams TJ, Levvey BJ, Russell PA, Milne DG, Snell GI (February 2003). "Interstitial pneumonitis associated with sirolimus: a dilemma for lung transplantation".
1116:
treated with sirolimus-eluting stents when compared to bare-metal stents, resulting in fewer repeat procedures. A sirolimus-eluting coronary stent was marketed by
5764:
Rivera VM, Clackson T, Natesan S, Pollock R, Amara JF, Keenan T, et al. (September 1996). "A humanized system for pharmacologic control of gene expression".
2177:
and that inhibiting mTOR with rapamycin may be a disease-modifying treatment. As of 2016 rapamycin had been tested in small clinical trials in people with lupus.
8955:
4426:
Gatto GJ, Boyne MT, Kelleher NL, Walsh CT (March 2006). "Biosynthesis of pipecolic acid by RapL, a lysine cyclodeaminase encoded in the rapamycin gene cluster".
2734:
9145:
1588:(FKBP12) in a manner similar to tacrolimus. Unlike the tacrolimus-FKBP12 complex, which inhibits calcineurin (PP2B), the sirolimus-FKBP12 complex inhibits the
3870:
Aparicio G, Calvo MB, Medina V, Fernández O, Jiménez P, Lema M, et al. (August 2009). "Comprehensive lung injury pathology induced by mTOR inhibitors".
182:
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9125:
3645:
3016:"Survival Associated With Sirolimus Plus Tacrolimus Maintenance Without Induction Therapy Compared With Standard Immunosuppression After Lung Transplant"
995:
is its low toxicity toward kidneys. Transplant patients maintained on calcineurin inhibitors long-term tend to develop impaired kidney function or even
5842:
5181:
4356:
Gregory MA, Hong H, Lill RE, Gaisser S, Petkovic H, Low L, et al. (October 2006). "Rapamycin biosynthesis: Elucidation of gene product function".
9794:
3079:
2876:
4846:
7481:
89:
8905:
2130:
8995:
5976:
Geeurickx M, Labarque V (September 2021). "A narrative review of the role of sirolimus in the treatment of congenital vascular malformations".
1225:
The following adverse effects occurred in 3–20% of individuals taking sirolimus for organ rejection prophylaxis following a kidney transplant:
3333:
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2471:
Text was copied from this source which is copyright
European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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1467:
There have been warnings about the use of sirolimus in transplants, where it may increase mortality due to an increased risk of infections.
1447:
Lung toxicity is a serious complication associated with sirolimus therapy, especially in the case of lung transplants. The mechanism of the
9814:
7345:
7203:
6046:
3740:
766:
5038:
A diverse and severe set of negative side effects likely preclude the wide-scale use of rapamycin and its analogs as a prolongevity agent.
3524:
Chhajed PN, Dickenmann M, Bubendorf L, Mayr M, Steiger J, Tamm M (2006). "Patterns of pulmonary complications associated with sirolimus".
2984:
954:
Sirolimus (Fyarro), as protein-bound particles, is indicated for the treatment of adults with locally advanced unresectable or metastatic
9306:
9185:
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7474:
7355:
7041:
6482:
3144:
2424:
9789:
9486:
9426:
4681:
4142:
Ferron GM, Mishina EV, Zimmerman JJ, Jusko WJ (April 1997). "Population pharmacokinetics of sirolimus in kidney transplant patients".
2591:"Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle"
9574:
9180:
9095:
5607:"New perspectives on the use of mTOR inhibitors in allogeneic haematopoietic stem cell transplantation and graft-versus-host disease"
907:. The compound was originally named rapamycin after the native name of the island, Rapa Nui. Sirolimus was initially developed as an
1592:(mammalian Target Of Rapamycin, rapamycin being another name for sirolimus) pathway by directly binding to mTOR Complex 1 (mTORC1).
9236:
6962:
5858:
5099:
3618:"Sirolimus-induced pneumonitis complicated by pentamidine-induced phospholipidosis in a renal transplant recipient: a case report"
1503:
Individuals taking sirolimus are at increased risk of experiencing impaired or delayed wound healing, particularly if they have a
8480:
8123:
2201:
4969:
2383:
2353:
2316:
1942:
polyketide, giving prerapamycin, the first enzyme-free product. The macrocyclic core is then customized by a series of post-PKS
5707:"Comprehensive analysis of the immunomodulatory effects of rapamycin on human T cells in graft-versus-host disease prophylaxis"
2529:
2956:
2917:
1900:
have been identified as coding for tailoring enzymes that modify the macrocyclic core to give rapamycin (figure 3). Finally,
5896:
Benjamin D, Colombi M, Moroni C, Hall MN (October 2011). "Rapamycin passes the torch: a new generation of mTOR inhibitors".
2962:
2923:
7616:
2494:
958:
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1459:
pathway. The interstitial pneumonitis is not dose-dependent, but is more common in patients with underlying lung disease.
999:; this can be avoided by using sirolimus instead. It is particularly advantageous in patients with kidney transplants for
4086:
Heitman J, Movva NR, Hall MN (August 1991). "Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast".
1596:
widely accepted name, since Tor was first discovered via genetic and molecular studies of sirolimus-resistant mutants of
1307:
5311:"Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial"
3474:"Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system"
1917:
ring of the starting unit is reduced during the transfer to module 1. The starting unit is then modified by a series of
9975:
8594:
4911:"Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis"
2726:
9985:
6905:
6275:
2105:
1215:
1072:
811:
786:
119:
106:
5420:"Rapamycin: A Bacteria-Derived Immunosuppressant That Has Anti-atherosclerotic Effects and Its Clinical Application"
2165:, thereby lowering the risk of atherosclerosis. Oxidized LDL cholesterol is a major contributor to atherosclerosis.
8939:
8014:
7540:
6039:
9714:
7314:
4499:"Regulating mammalian target of rapamycin to tune vaccination-induced CD8(+) T cell responses for tumor immunity"
2213:
1773:
1716:
1048:
861:
350:
242:
70:
5811:"Study to assess healthy aging in dogs: the Dog Aging Project and Test of Rapamycin in Aging Dogs (TRIAD study)"
4391:
Graziani EI (May 2009). "Recent advances in the chemistry, biosynthesis and pharmacology of rapamycin analogs".
9950:
9396:
3617:
2807:
Pritchard DI (May 2005). "Sourcing a chemical succession for cyclosporin from parasites and human pathogens".
2158:
1589:
774:
O1CC(C1OC)C(C)4CC(=O)(C)/C=C(\C)(O)(OC)C(=O)(C)C(C)\C=C\C=C\C=C(/C)(OC)C2CC(C)(O)(O2)C(=O)C(=O)N3CCCC3C(=O)O4
5834:
5173:
2173:
As of 2016, studies in cells, animals, and humans have suggested that mTOR activation as process underlying
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8360:
6111:
3075:
3071:
2988:
2848:
2174:
920:
671:
524:
3101:
Shuchman M (November 2006). "Trading restenosis for thrombosis? New questions about drug-eluting stents".
986:
9955:
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6032:
4838:
3567:
Morelon E, Stern M, Israël-Biet D, Correas JM, Danel C, Mamzer-Bruneel MF, et al. (September 2001).
2261:"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)"
2006:. However, these drugs have a higher rate of fatal adverse events in cancer patients than control drugs.
1483:. In studies, the skin cancer risk under sirolimus was lower than under other immunosuppressants such as
632:
7466:
5509:"Activation of the Mechanistic Target of Rapamycin in SLE: Explosion of Evidence in the Last Five Years"
3923:
Paris A, Goupil F, Kernaonet E, Foulet-Rogé A, Molinier O, Gagnadoux F, et al. (January 2012). "".
2196:
Due to its immunosuppressant activity, Rapamycin has been assessed as prophylaxis or treatment agent of
9920:
8666:
8515:
8264:
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6090:
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2058:
1040:
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1000:
84:
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9824:
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8001:
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7148:
3960:"Drug-related pneumonitis in patients with advanced renal cell carcinoma treated with temsirolimus"
3616:
Filippone EJ, Carson JM, Beckford RA, Jaffe BC, Newman E, Awsare BK, et al. (September 2011).
2842:
1834:
encode for three extremely large and complex multienzymes, RapA, RapB, and RapC, respectively. The
1598:
1448:
1063:
1032:
948:
911:
agent. However, this use was abandoned when it was discovered to have potent immunosuppressive and
845:
648:
3472:
Arriola Apelo SI, Neuman JC, Baar EL, Syed FA, Cummings NE, Brar HK, et al. (February 2016).
1097:
The safety of LAM treatment by sirolimus in people younger than 18 years old has not been tested.
7497:
7143:
5052:"Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects"
2025:
in mice. Akt signalling promotes cell survival in Akt-positive lymphomas and acts to prevent the
1999:
1966:
A plaque, written in
Portuguese, commemorating the discovery of sirolimus on Easter Island, near
1377:
1187:
160:
52:
1933:, the growing polyketide is further modified according to enzymatic domains that are present to
1798:
Figure 4: Proposed mechanism of lysine cyclodeaminase conversion of L-lysine to L-pipecolic acid
1669:
9386:
9015:
8369:
7852:
7581:
6948:
6374:
6055:
3717:
3569:"Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients"
3248:
Triana P, Dore M, Cerezo VN, Cervantes M, Sánchez AV, Ferrero MM, et al. (February 2017).
1629:
around 60 hours +/- 10 hours. Sirolimus was not found to effect the concentration of
1275:
1267:
614:
297:
175:
5935:"Efficacy and safety of sirolimus in the treatment of vascular anomalies: A systematic review"
3368:"Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity"
513:
9970:
7927:
7867:
7837:
7740:
7576:
7135:
5309:
Chung CL, Lawrence I, Hoffman M, Elgindi D, Nadhan K, Potnis M, et al. (December 2019).
5050:
Strong R, Miller RA, Bogue M, Fernandez E, Javors MA, Libert S, et al. (November 2020).
3366:
Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, et al. (March 2012).
3014:
Wijesinha M, Hirshon JM, Terrin M, Magder L, Brown C, Stafford K, et al. (August 2019).
2416:
1818:
responsible for rapamycin synthesis have been identified. As expected, three extremely large
1626:
1558:
1534:, whereas inducers of CYP3A4 and P-gp may decrease sirolimus concentrations in blood plasma.
1488:
1015:
1007:
992:
936:
908:
573:
9231:
9221:
5933:
Freixo C, Ferreira V, Martins J, Almeida R, Caldeira D, Rosa M, et al. (January 2020).
4261:
Schwecke T, Aparicio JF, Molnár I, König A, Khaw LE, Haydock SF, et al. (August 1995).
3667:
Pham PT, Pham PC, Danovitch GM, Ross DJ, Gritsch HA, Kendrick EA, et al. (April 2004).
9569:
9541:
9531:
9150:
7782:
7677:
7514:
5469:
Stocker R, Keaney JF (October 2004). "Role of oxidative modifications in atherosclerosis".
5374:
5216:
4796:
4274:
4095:
3379:
2451:
2041:. Sirolimus blocks Akt signalling and the cells lose their resistance to the chemotherapy.
2022:
2003:
1926:
1918:
1381:
1326:
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1121:
1036:
533:
448:
319:
171:
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4673:
4625:"A new role for sirolimus: regression of Kaposi's sarcoma in kidney-transplant recipients"
4497:
Li Q, Rao R, Vazzana J, Goedegebuure P, Odunsi K, Gillanders W, et al. (April 2012).
4035:
Euvrard S, Morelon E, Rostaing L, Goffin E, Brocard A, Tromme I, et al. (July 2012).
1787:
Figure 3: Sequence of "tailoring" steps, which convert unbound prerapamycin into rapamycin
225:
8:
9965:
9371:
9271:
9195:
8897:
8635:
7902:
7892:
7712:
6356:
3958:
Maroto JP, Hudes G, Dutcher JP, Logan TF, White CS, Krygowski M, et al. (May 2011).
2225:
2010:
1983:
1819:
1769:
1712:
439:
167:
9565:
6018:
for "A Phase 2 Study of ABI-009 in
Patients With Advanced Malignant PEComa (AMPECT)" at
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4800:
4278:
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3383:
292:
14% (oral solution), lower with high-fat meals; 18% (tablet), higher with high-fat meals
9844:
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7827:
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5921:
5789:
5746:
5687:
5633:
5582:
5557:
5533:
5508:
5446:
5395:
5362:
5335:
5310:
5286:
5261:
5237:
5204:
5154:
5076:
5051:
5024:
4999:
4937:
4910:
4891:
4820:
4764:
4740:"Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer"
4739:
4654:
4571:
4523:
4498:
4238:
4190:
4119:
4013:
3905:
3698:
3633:
3598:
3549:
3498:
3473:
3449:
3424:
3400:
3367:
3315:
3042:
3032:
3015:
2784:
2757:
2702:
2228:
2142:
1271:
1150:
1106:
970:
880:
675:
652:
134:
5705:
Ehx G, Ritacco C, Hannon M, Dubois S, Delens L, Willems E, et al. (August 2021).
4155:
3848:
3685:
3668:
2820:
2564:
9980:
9549:
9256:
7967:
7310:
7300:
6101:
6059:
5993:
5968:
5956:
5913:
5781:
5750:
5738:
5679:
5638:
5587:
5558:"Efficacy of sirolimus in children with lymphatic malformations of the head and neck"
5538:
5486:
5451:
5400:
5340:
5291:
5242:
5158:
5146:
5081:
5029:
4961:
4942:
4812:
4769:
4720:
4658:
4646:
4606:
4602:
4563:
4528:
4479:
4475:
4443:
4408:
4373:
4338:
4302:
4297:
4230:
4226:
4194:
4159:
4111:
4068:
4017:
3981:
3940:
3897:
3852:
3817:
3782:
3732:
3690:
3637:
3590:
3585:
3568:
3541:
3503:
3454:
3405:
3307:
3271:
3230:
3189:
3118:
3047:
2952:
2913:
2824:
2789:
2707:
2612:
2568:
2551:
Simamora P, Alvarez JM, Yalkowsky SH (February 2001). "Solubilization of rapamycin".
2146:
2134:
1910:
1873:
912:
853:
604:
5793:
5691:
4895:
4575:
4242:
3909:
3702:
3602:
3553:
2521:
1962:
473:
9960:
9834:
9554:
9436:
9366:
9251:
9241:
9155:
9005:
7807:
7649:
7644:
7106:
7009:
6672:
6568:
5985:
5946:
5925:
5905:
5773:
5728:
5718:
5669:
5628:
5618:
5577:
5569:
5528:
5520:
5478:
5441:
5431:
5390:
5382:
5330:
5322:
5281:
5273:
5232:
5224:
5138:
5071:
5063:
5019:
5011:
4932:
4922:
4881:
4824:
4804:
4759:
4751:
4712:
4636:
4598:
4555:
4518:
4510:
4471:
4435:
4400:
4365:
4330:
4292:
4282:
4222:
4186:
4151:
4123:
4103:
4058:
4048:
4009:
3971:
3932:
3887:
3879:
3844:
3809:
3774:
3680:
3629:
3580:
3533:
3493:
3485:
3444:
3436:
3395:
3387:
3319:
3299:
3261:
3220:
3179:
3110:
3037:
3027:
2816:
2779:
2769:
2697:
2687:
2602:
2560:
2038:
1807:
1428:
1286:
1199:
1167:
1117:
1084:
1019:
753:
688:
279:
215:
205:
195:
6014:
4716:
2758:"Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer"
9934:
9511:
9406:
9286:
7405:
7290:
5674:
5657:
5363:"Rapamycin as a potential repurpose drug candidate for the treatment of COVID-19"
5142:
3813:
3778:
3425:"Sirolimus is associated with new-onset diabetes in kidney transplant recipients"
2946:
2907:
2062:
1689:
1642:
1548:
1504:
1341:
1211:
1128:. However, this kind of stent may also increase the risk of vascular thrombosis.
1111:
The antiproliferative effect of sirolimus has also been used in conjunction with
1018:, to provide steroid-free immunosuppression regimens. Impaired wound healing and
982:
944:
916:
841:
307:
287:
2483:"Immunosuppression With Sirolimus After Solid Organ Transplantation in Children"
2482:
1752:
Figure 1: Domain organization of PKS of rapamycin and biosynthetic intermediates
39:
9859:
9779:
9649:
9506:
9361:
9326:
8985:
8744:
8642:
8590:
8188:
7501:
7295:
7163:
6811:
6645:
6624:
6620:
6616:
6244:
6081:
5989:
5573:
5482:
5326:
5004:
The
Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
4267:
Proceedings of the National Academy of Sciences of the United States of America
2607:
2590:
2232:
2185:
2138:
2101:
2097:
1987:
1854:
1618:
1530:; hence, inhibitors of either protein may increase sirolimus concentrations in
1523:
1393:
1262:
1254:
1112:
1059:
996:
837:
5951:
5934:
5524:
5386:
4927:
4263:"The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin"
3936:
3883:
3225:
3208:
3184:
3167:
2065:
in adults, many US doctors began prescribing sirolimus (Wyeth's Rapamune) and
1794:
9944:
9799:
9674:
9559:
9521:
9416:
9381:
9316:
9115:
9075:
8975:
8801:
8691:
8653:
8630:
8562:
8557:
8547:
8323:
8319:
8307:
8114:
7897:
7862:
7682:
7662:
7445:
7375:
7285:
7192:
6978:
6678:
6600:
6552:
6532:
6390:
6306:
6157:
6123:
5436:
5419:
5100:"Late-Life Rapamycin Regimens Extend Mouse Lifespan in a Sex-Specific Manner"
4650:
4514:
3976:
3959:
2109:
1250:
1157:
In April 2022, sirolimus was approved by the FDA for treating angiofibromas.
1052:
904:
873:
664:
257:
5015:
4287:
4262:
4107:
3391:
2676:"A comprehensive review of immunosuppression used for liver transplantation"
1781:
856:
functions in humans and is especially useful in preventing the rejection of
9884:
9854:
9829:
9784:
9729:
9724:
9709:
9704:
9694:
9689:
9614:
9516:
9496:
9481:
9476:
9471:
9456:
9351:
9341:
9170:
9110:
9045:
9040:
9035:
9030:
9010:
9000:
8841:
8826:
8796:
8776:
8658:
8606:
8567:
8455:
8434:
8341:
8303:
8204:
8179:
8175:
8059:
8024:
7977:
7962:
7917:
7792:
7762:
7687:
7505:
7455:
7415:
7400:
7395:
7111:
7061:
7056:
7036:
6916:
6911:
6774:
6759:
6707:
6683:
6630:
6507:
6497:
6316:
6233:
6228:
6186:
6139:
6096:
6063:
5997:
5960:
5917:
5742:
5642:
5591:
5542:
5490:
5455:
5404:
5344:
5295:
5246:
5150:
5085:
5033:
4946:
4909:
Li M, Zhou Y, Chen C, Yang T, Zhou S, Chen S, et al. (February 2019).
4816:
4773:
4755:
4724:
4610:
4567:
4559:
4532:
4447:
4412:
4377:
4342:
4334:
4234:
4198:
4072:
4021:
3985:
3944:
3901:
3856:
3821:
3786:
3736:
3694:
3641:
3594:
3545:
3507:
3458:
3440:
3409:
3311:
3275:
3266:
3249:
3234:
3193:
3122:
3051:
2828:
2793:
2774:
2711:
2637:
2572:
2030:
1991:
1930:
1929:(ACP) and extend the polyketide by two carbons each. After each successive
1729:
1720:
1708:
1531:
1484:
1436:
1397:
1179:
1146:
1125:
1058:
The safety and efficacy of sirolimus treatment of LAM were investigated in
966:
924:
220:
210:
200:
190:
5785:
5683:
4483:
4306:
4163:
4115:
4053:
4037:"Sirolimus and secondary skin-cancer prevention in kidney transplantation"
4036:
3718:"Sirolimus-induced interstitial pneumonitis in a renal transplant patient"
2692:
2675:
2616:
1573:. Ciclosporin and tacrolimus inhibit the secretion of IL-2, by inhibiting
22:
9869:
9839:
9819:
9769:
9644:
9639:
9624:
9594:
9421:
9376:
9336:
9331:
9281:
9276:
9261:
9100:
9060:
8965:
8871:
8851:
8846:
8836:
8816:
8791:
8786:
8769:
8717:
8707:
8702:
8697:
8599:
8526:
8496:
8491:
8486:
8470:
8460:
8440:
8315:
8311:
8299:
8295:
8224:
8128:
8074:
8069:
8034:
7972:
7957:
7947:
7942:
7937:
7932:
7912:
7877:
7832:
7812:
7802:
7757:
7722:
7702:
7658:
7621:
7609:
7604:
7566:
7550:
7496:
7450:
7390:
7380:
7370:
7270:
7260:
7250:
7245:
7210:
7121:
7116:
7091:
7081:
7071:
7046:
7031:
7026:
6984:
6954:
6940:
6935:
6921:
6864:
6822:
6817:
6803:
6798:
6784:
6764:
6717:
6693:
6651:
6635:
6606:
6590:
6558:
6542:
6537:
6512:
6462:
6452:
6447:
6442:
6431:
6421:
6326:
6238:
6196:
6181:
6175:
6171:
6118:
5000:"Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island"
2162:
2081:
2034:
2014:
1947:
1914:
1864:, which is embedded between the PKS genes and translationally coupled to
1693:
1630:
1622:
1574:
1527:
1476:
1405:
1354:
1330:
1298:
1279:
1091:
1076:
940:
5777:
5228:
4808:
4641:
4624:
3114:
1762:
1657:
493:
9849:
9809:
9754:
9744:
9684:
9669:
9654:
9634:
9609:
9604:
9584:
9579:
9536:
9526:
9491:
9466:
9446:
9411:
9390:
9346:
9321:
9105:
9070:
9055:
9050:
9019:
8980:
8960:
8886:
8881:
8856:
8821:
8806:
8781:
8764:
8754:
8712:
8683:
8648:
8614:
8531:
8521:
8501:
8465:
8450:
8445:
8415:
8349:
8345:
8327:
8275:
8254:
8214:
8209:
8148:
8079:
8054:
8029:
7952:
7887:
7847:
7842:
7822:
7817:
7797:
7787:
7777:
7692:
7672:
7654:
7562:
7440:
7435:
7420:
7360:
7350:
7335:
7330:
7325:
7275:
7265:
7255:
7220:
7198:
7184:
7096:
7086:
7076:
7066:
7051:
6994:
6989:
6968:
6883:
6878:
6836:
6830:
6731:
6688:
6584:
6574:
6527:
6517:
6492:
6487:
6477:
6472:
6467:
6457:
6416:
6401:
6396:
6380:
6321:
6301:
6250:
6210:
6191:
6133:
5733:
5655:
5067:
4589:
Law BK (October 2005). "Rapamycin: an anti-cancer immunosuppressant?".
4063:
3489:
3166:
Dekeuleneer V, Seront E, Van Damme A, Boon LM, Vikkula M (April 2020).
2317:"Rapamune- sirolimus solution Rapamune- sirolimus tablet, sugar coated"
2090:
2066:
1995:
1909:
4,5-dihydroxocyclohex-1-ene-carboxylic acid, which is derived from the
1803:
1733:
1724:
1554:
1432:
1401:
1388:
1315:
1291:
1246:
1207:
1195:
1183:
1071:, abdominal pain, nausea, sore throat, acne, chest pain, leg swelling,
1011:
884:
718:
504:
6054:
5723:
5706:
5656:
Blazar BR, Taylor PA, Panoskaltsis-Mortari A, Vallera DA (June 1998).
5623:
5606:
4439:
4256:
4254:
4252:
3892:
3537:
3361:
3359:
3334:"FDA Approves Nobelpharma's Topical Treatment for Facial Angiofibroma"
3303:
30:
9764:
9759:
9749:
9734:
9719:
9664:
9619:
9589:
9451:
9431:
9356:
9296:
9291:
9160:
9090:
9080:
9025:
8876:
8866:
8861:
8831:
8811:
8759:
8749:
8737:
8732:
8678:
8673:
8619:
8552:
8425:
8420:
8405:
8400:
8395:
8385:
8380:
8375:
8280:
8270:
8249:
8244:
8239:
8234:
8229:
8219:
8199:
8163:
8158:
8153:
8143:
8138:
8105:
8100:
8095:
8064:
8044:
8039:
7882:
7872:
7697:
7545:
7430:
7425:
7410:
7385:
7340:
7320:
7280:
7215:
7179:
7101:
6897:
6850:
6779:
6745:
6712:
6522:
6502:
6411:
6151:
4404:
4369:
2236:
2026:
1951:
1938:
1363:
1359:
1302:
955:
923:(FDA) in September 1999. Hyftor was approved for treatment of facial
833:
459:
332:
5909:
5277:
4886:
4869:
9679:
9659:
9629:
9501:
9461:
9311:
9301:
9175:
8626:
8390:
8194:
8133:
8089:
8049:
8019:
7772:
7636:
7632:
7557:
7365:
7240:
6929:
6437:
6347:
6283:
6205:
4249:
3356:
1967:
1480:
1373:
1347:
1334:
1068:
891:
553:
484:
101:
5128:
4546:
Easton JB, Houghton PJ (October 2006). "mTOR and cancer therapy".
3799:
2354:"Fyarro- sirolimus injection, powder, lyophilized, for suspension"
1479:
from exposure to sunlight or UV radiation, and risk of developing
1174:, abdominal pain, headache, nausea, diarrhea, pain, constipation,
741:
620:
9889:
9874:
9804:
9266:
8990:
7730:
6858:
1943:
1922:
1696:
1581:
1492:
1219:
1090:
While sirolimus was considered for treatment of LAM, it received
869:
865:
4211:
3764:
2141:
seen in very serious cases of COVID-19. Moreover, inhibition of
1079:. Serious side effects including hypersensitivity and swelling (
7173:
7004:
4786:
3922:
1869:
1857:(figure 4) for incorporation at the end of the polyketide. The
1850:
1846:
1634:
1614:
1611:
1570:
1566:
1519:
1516:
1424:
1420:
1242:
1191:
1051:
signaling pathway, resulting in the release of lymphangiogenic
857:
584:
3566:
3523:
3292:
Journal of the European Academy of Dermatology and Venereology
3165:
3072:"FDA approves Rapamune to treat LAM, a very rare lung disease"
2045:-positive lymphomas were completely resistant to the therapy;
88:
8610:
8336:
8170:
8119:
7599:
6872:
6725:
5859:"Dog aging project - TRIAD (Test of Rapamycin in Aging Dogs)"
3998:
2046:
2042:
1934:
1842:
1815:
1080:
899:
and was isolated for the first time in 1972, from samples of
732:
564:
312:
5932:
5763:
5507:
Oaks Z, Winans T, Huang N, Banki K, Perl A (December 2016).
5259:
5202:
4034:
3869:
3834:
3615:
3013:
2641:
1475:
Sirolimus may increase an individual's risk for contracting
637:
8725:
8511:
8009:
7735:
7717:
7707:
7667:
7535:
6844:
6792:
6753:
6739:
6293:
6167:
5978:
Journal of Vascular Surgery. Venous and Lymphatic Disorders
5308:
5205:"mTOR is a key modulator of ageing and age-related disease"
4460:
4260:
4141:
3471:
3365:
3288:
2077:
1858:
1835:
1585:
1562:
1456:
1455:
inhibitors is unclear, and may have nothing to do with the
1452:
1044:
1006:
Sirolimus can also be used alone, or in conjunction with a
544:
8927:
5049:
1872:, an NPRS responsible for incorporating L-pipecolic acid,
6701:
5895:
5203:
Johnson SC, Rabinovitch PS, Kaeberlein M (January 2013).
3247:
2843:"Drug Approval Package: Rapamune (Sirolimus) NDA# 021083"
2268:
2240:
2104:
decreases, which suggests an immunostimulatory response,
2096:
Sirolimus has complex effects on the immune system—while
2018:
1982:
Sirolimus was shown to inhibit the progression of dermal
1462:
1423:
appears to mediate the drug's benefits, it also inhibits
8940:
5839:
Washington State University Veterinary Teaching Hospital
4496:
2550:
1668: with: content on this topic from . You can help by
864:(mTOR) kinase inhibitor that reduces the sensitivity of
5260:
Weichhart T, Hengstschläger M, Linke M (October 2015).
4425:
3957:
3422:
1732:
of the linear polyketide are in RapC. Then, the linear
5704:
4355:
4319:
4176:
3526:
Respiration; International Review of Thoracic Diseases
3423:
Johnston O, Rose CL, Webster AC, Gill JS (July 2008).
2909:
Drug Discovery: Practices, Processes, and Perspectives
2724:
2212:
Rapamycin is used in biology research as an agent for
2049:-expressing lymphomas are not sensitive to sirolimus.
1998:(RAD001), are being tested for use in cancers such as
1925:
or methylmalonyl substrates, which are attached to an
9918:
3666:
2311:
2309:
2307:
2305:
976:
5863:
Iowa State University College of Veterinary Medicine
5815:
University of Georgia College of Veterinary Medicine
5555:
5506:
4997:
4702:
4137:
4135:
4133:
2588:
2303:
2301:
2299:
2297:
2295:
2293:
2291:
2289:
2287:
2285:
1876:
and cyclization of prerapamycin. In addition, genes
1094:
designation status because LAM is a rare condition.
5262:"Regulation of innate immune cell function by mTOR"
5174:"Can a Kidney Transplant Drug Keep You From Aging?"
2516:
2514:
2512:
2253:
2207:
4839:"Combination therapy drives cancer into remission"
3250:"Sirolimus in the Treatment of Vascular Anomalies"
3209:"Sirolimus in the treatment of vascular anomalies"
2673:
2348:
2346:
2344:
2342:
1711:of the rapamycin core is accomplished by a type I
1145:Sirolimus has been used as a topical treatment of
5975:
4130:
2948:Nanotechnology in Medicine: Emerging Applications
2669:
2667:
2665:
2663:
2661:
2659:
2528:. National Center for Biotechnology Information.
2282:
1507:in excess of 30 kg/m (classified as obese).
1031:In May 2015, the FDA approved sirolimus to treat
9942:
4861:
4384:
4085:
3168:"Theranostic Advances in Vascular Malformations"
2725:Qari S, Walters P, Lechtenberg S (21 May 2021).
2589:Vézina C, Kudelski A, Sehgal SN (October 1975).
2509:
1075:, headache, dizziness, muscle pain and elevated
472:
5360:
5356:
5354:
4993:
4991:
4989:
4987:
4349:
2800:
2411:
2409:
2376:
2339:
2131:severe acute respiratory syndrome coronavirus 2
2129:Rapamycin has been proposed as a treatment for
1580:The mode of action of sirolimus is to bind the
879:This compound also has a use in cardiovascular
447:
430:conta-16,24,26,28-tetraene-2,3,10,14,20-pentone
5556:Wiegand S, Dietz A, Wichmann G (August 2022).
5502:
5500:
4908:
4545:
2656:
118:
8913:
7482:
6040:
5468:
3837:The Journal of Heart and Lung Transplantation
3802:The Journal of Heart and Lung Transplantation
3767:The Journal of Heart and Lung Transplantation
3519:
3517:
3429:Journal of the American Society of Nephrology
2446:
2444:
2442:
2052:
1633:, which is also metabolized primarily by the
987:Immunosuppression § Deliberately induced
426:19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-
5462:
5417:
5411:
5351:
5043:
4984:
4780:
4674:"Fatal AEs Higher with mTOR Drugs in Cancer"
4313:
4170:
4079:
3326:
3241:
3200:
3159:
2406:
2191:
1047:). Loss of TSC2 gene function activates the
105:
9196:
5497:
3065:
3063:
3061:
2674:Mukherjee S, Mukherjee U (1 January 2009).
1768:Figure 2: Prerapamycin, unbound product of
1728:and the final four modules to complete the
1026:
224:
9247:Allopregnanedione (5α-dihydroprogesterone)
8920:
8906:
7489:
7475:
6047:
6033:
5604:
5562:European Archives of Oto-Rhino-Laryngology
4998:Arriola Apelo SI, Lamming DW (July 2016).
3715:
3514:
2439:
1986:in patients with renal transplants. Other
674:
651:
512:
5950:
5732:
5722:
5673:
5632:
5622:
5581:
5532:
5445:
5435:
5394:
5334:
5285:
5236:
5075:
5023:
4936:
4926:
4885:
4763:
4640:
4522:
4454:
4296:
4286:
4062:
4052:
3975:
3891:
3684:
3669:"Sirolimus-associated pulmonary toxicity"
3584:
3497:
3448:
3399:
3265:
3224:
3183:
3041:
3031:
2985:"Sirolimus (marketed as Rapamune) Safety"
2944:
2806:
2783:
2773:
2701:
2691:
2634:"Cypher Sirolimus-eluting Coronary Stent"
2628:
2626:
2606:
2235:examining the effect of rapamycin on the
2180:
2115:
2057:Sirolimus also shows promise in treating
1498:
1414:
1131:
1100:
1062:that compared sirolimus treatment with a
532:
8945:Tooltip Constitutive androstane receptor
5611:British Journal of Clinical Pharmacology
5361:Husain A, Byrareddy SN (November 2020).
4671:
4428:Journal of the American Chemical Society
4390:
3172:The Journal of Investigative Dermatology
3100:
3094:
3058:
2157:Rapamycin can accelerate degradation of
1961:
1793:
1719:(NRPS). The domains responsible for the
1451:caused by sirolimus and other macrolide
1023:of a number of ongoing clinical trials.
4591:Critical Reviews in Oncology/Hematology
4582:
2905:
2584:
2582:
2202:hematopoietic stem cell transplantation
2072:
991:The chief advantage sirolimus has over
647:
492:
9943:
9700:Pregnanedione (5β-dihydroprogesterone)
9086:Pregnanedione (5β-dihydroprogesterone)
4144:Clinical Pharmacology and Therapeutics
2995:from the original on 16 September 2016
2965:from the original on 30 September 2020
2727:"The Dirty Drug and the Ice Cream Tub"
2623:
2553:International Journal of Pharmaceutics
2017:and sirolimus has been shown to drive
1463:Lowered effectiveness of immune system
665:
266:
79:
8901:
7470:
6028:
5869:from the original on 23 February 2023
5845:from the original on 23 February 2023
5821:from the original on 23 February 2023
5171:
5110:from the original on 28 February 2021
4867:
4684:from the original on 28 February 2021
3872:Clinical & Translational Oncology
3254:European Journal of Pediatric Surgery
3069:
2887:from the original on 27 November 2021
2364:from the original on 19 December 2021
2327:from the original on 27 November 2021
613:
592:
572:
251:
113:
96:
4737:
4731:
4358:Organic & Biomolecular Chemistry
3716:Mingos MA, Kane GC (December 2005).
2857:from the original on 1 February 2022
2755:
2579:
2480:
2137:effects could prevent or reduce the
1652:
959:perivascular epithelioid cell tumour
850:perivascular epithelioid cell tumour
619:
214:
204:
194:
5711:American Journal of Transplantation
5418:Liu Y, Yang F, Zou S, Qu L (2019).
4588:
4041:The New England Journal of Medicine
3206:
3103:The New England Journal of Medicine
3082:from the original on 14 August 2016
2926:from the original on 19 August 2020
2883:(Press release). 23 November 2021.
2762:Clinical and Translational Medicine
2532:from the original on 16 August 2016
2427:from the original on 13 August 2021
1841:has been established to code for a
1605:
1565:, and thereby blocks activation of
1542:
1308:Thrombotic thrombocytopenic purpura
927:in the European Union in May 2023.
876:(IL-2), inhibiting their activity.
844:, treat a rare lung disease called
552:
463:
13:
5888:
5605:Lutz M, Mielke S (November 2016).
4959:
4191:10.1097/01.ftd.0000179838.33020.34
4014:10.1016/j.transproceed.2010.07.066
3648:from the original on 7 August 2020
3634:10.1016/j.transproceed.2011.06.060
3033:10.1001/jamanetworkopen.2019.10297
2497:from the original on 18 April 2020
2394:from the original on 24 March 2022
2219:
2152:
1160:
1039:-like cells with mutations of the
977:Prevention of transplant rejection
14:
10007:
6006:
5104:Nicotinamide Mononucleotide (NMN)
4972:from the original on 25 July 2021
4915:Orphanet Journal of Rare Diseases
3686:10.1097/01.TP.0000118413.92211.B6
3137:"Venous Malformation: Treatments"
2737:from the original on 25 July 2021
2231:are participating in a long-term
1216:upper respiratory tract infection
1073:upper respiratory tract infection
1055:. Sirolimus blocks this pathway.
428:11,36-dioxa-4-azatricyclohexatria
145:
9928:
4849:from the original on 1 June 2022
4629:Nature Clinical Practice Urology
4603:10.1016/j.critrevonc.2004.09.009
4227:10.1097/00007691-200206000-00004
3925:Revue des Maladies Respiratoires
3746:from the original on 5 June 2022
3586:10.1097/00007890-200109150-00008
3344:from the original on 1 June 2022
2906:Li JJ, Corey EJ (3 April 2013).
2208:Applications in biology research
1780:
1761:
1741:
1656:
1610:Sirolimus is metabolized by the
1515:Sirolimus is metabolized by the
1442:
1140:
705:
699:
38:
29:
5835:"Dog Aging Project TRIAD Study"
5800:
5757:
5698:
5649:
5598:
5549:
5367:Chemico-Biological Interactions
5302:
5253:
5196:
5184:from the original on 8 May 2023
5165:
5122:
5092:
4953:
4902:
4870:"Therapeutics: Means to an end"
4831:
4696:
4672:Bankhead C (17 February 2013).
4665:
4617:
4539:
4490:
4419:
4205:
4028:
3992:
3951:
3916:
3863:
3828:
3793:
3758:
3709:
3660:
3609:
3560:
3465:
3416:
3282:
3129:
3007:
2977:
2945:Koprowski G (7 February 2012).
2938:
2899:
2869:
2835:
2749:
2718:
2214:chemically induced dimerization
1849:cycloamidase, which converts L-
1717:nonribosomal peptide synthetase
1702:
1537:
1510:
930:
862:mechanistic target of rapamycin
799:Key:QFJCIRLUMZQUOT-HPLJOQBZSA-N
9252:Allopregnanolone (brexanolone)
5898:Nature Reviews. Drug Discovery
5131:Science Translational Medicine
2544:
2474:
1954:by P-450s to yield rapamycin.
1470:
1419:While sirolimus inhibition of
919:. It was approved by the U.S.
836:compound that is used to coat
828:and sold under the brand name
708:
693:
1:
9907:Receptor/signaling modulators
9865:Tropanyl 3,5-dimethulbenzoate
9715:Pregnenolone 16α-carbonitrile
4843:Cold Spring Harbor Laboratory
4717:10.1158/0008-5472.CAN-05-0917
4156:10.1016/S0009-9236(97)90192-2
3849:10.1016/S1053-2498(02)00564-8
2821:10.1016/S1359-6446(05)03395-7
2565:10.1016/s0378-5173(00)00617-7
2246:
2124:
6112:dihydroorotate dehydrogenase
5675:10.4049/jimmunol.160.11.5355
5513:Current Rheumatology Reports
5143:10.1126/scitranslmed.3009892
4476:10.1016/0378-1119(95)00800-4
3964:Journal of Clinical Oncology
3814:10.1016/j.healun.2006.05.013
3779:10.1016/j.healun.2006.12.004
3076:Food and Drug Administration
2989:Food and Drug Administration
2849:Food and Drug Administration
2175:systemic lupus erythematosus
1868:, encodes for an additional
1715:(PKS) in conjunction with a
1648:
1325:Abnormal healing, increased
921:Food and Drug Administration
7:
9442:Dodecylbenzenesulfonic acid
9201:Tooltip Pregnane X receptor
8929:Xenobiotic-sensing receptor
6091:purine synthesis inhibitors
5939:Journal of Vascular Surgery
4215:Therapeutic Drug Monitoring
4179:Therapeutic Drug Monitoring
4002:Transplantation Proceedings
3622:Transplantation Proceedings
3213:Journal of Vascular Surgery
1957:
1553:Unlike the similarly named
10:
10012:
7992:Tyrosine kinase inhibitors
5990:10.1016/j.jvsv.2021.03.001
5574:10.1007/s00405-022-07378-8
5483:10.1152/physrev.00047.2003
5327:10.1007/s11357-019-00113-y
5266:Nature Reviews. Immunology
3141:Boston Children's Hospital
2680:Journal of Transplantation
2608:10.7164/antibiotics.28.721
2595:The Journal of Antibiotics
2200:(GVHD), a complication of
2145:by rapamycin could reduce
2059:tuberous sclerosis complex
2053:Tuberous sclerosis complex
1617:and is a substrate of the
1546:
1522:and is a substrate of the
1104:
1041:tuberous sclerosis complex
980:
945:organ transplant rejection
901:Streptomyces hygroscopicus
896:Streptomyces hygroscopicus
842:organ transplant rejection
683:Chemical and physical data
9976:Drugs developed by Pfizer
9898:
9194:
8938:
8582:
8359:
8000:
7990:
7858:Mirvetuximab soravtansine
7750:
7631:
7591:
7526:
7513:
7233:
7161:
7134:
7019:
6662:
6364:
6355:
6346:
6339:
6292:
6276:IL-1 receptor antagonists
6274:
6265:
6219:
6150:
6080:
6071:
5952:10.1016/j.jvs.2019.06.217
5525:10.1007/s11926-016-0622-8
5424:Frontiers in Pharmacology
5387:10.1016/j.cbi.2020.109282
4928:10.1186/s13023-019-1012-x
4744:British Journal of Cancer
3937:10.1016/j.rmr.2010.03.026
3884:10.1007/s12094-009-0394-y
3226:10.1016/j.jvs.2019.08.246
3185:10.1016/j.jid.2019.10.001
2912:. John Wiley & Sons.
2487:Pediatric Pharmacotherapy
2457:European Medicines Agency
2421:European Medicines Agency
2198:Graft-versus-host disease
2192:Graft-versus-host disease
2021:-positive lymphomas into
1973:
1312:hemolytic uremic syndrome
1001:hemolytic-uremic syndrome
947:and for the treatment of
807:
782:
762:
752:
730:
717:
687:
682:
663:
631:
603:
583:
563:
543:
523:
503:
483:
458:
438:
346:
341:
331:
318:
306:
296:
286:
278:
241:
236:
181:
159:
133:
69:
61:
51:
46:
37:
28:
9986:Drugs developed by Wyeth
9825:Testosterone isocaproate
9740:Reverse triiodothyronine
8002:Receptor tyrosine kinase
7528:Receptor tyrosine kinase
7149:Anti-lymphocyte globulin
5437:10.3389/fphar.2018.01520
4515:10.4049/jimmunol.1103365
3977:10.1200/JCO.2010.29.2235
2756:Seto B (November 2012).
2168:
2159:oxidized LDL cholesterol
1599:Saccharomyces cerevisiae
1449:interstitial pneumonitis
1083:) have been observed in
1033:lymphangioleiomyomatosis
1027:Lymphangioleiomyomatosis
949:lymphangioleiomyomatosis
883:technologies to inhibit
846:lymphangioleiomyomatosis
57:Rapamune, Fyarro, Hyftor
9217:17α-Hydroxyprogesterone
9212:17α-Hydroxypregnenolone
7592:Others for solid tumors
7498:Targeted cancer therapy
7144:Anti-thymocyte globulin
6056:Immunosuppressive drugs
4738:Chan S (October 2004).
4393:Natural Product Reports
4288:10.1073/pnas.92.17.7839
4108:10.1126/science.1715094
3392:10.1126/science.1215135
3207:Lee BB (January 2020).
3070:Pahon E (28 May 2015).
2384:"Hyftor- sirolimus gel"
2000:glioblastoma multiforme
1491:, and lower than under
1400:, menstrual disorders (
1378:squamous cell carcinoma
1188:urinary tract infection
917:ability to inhibit mTOR
420:)-1,18-dihydroxy-12-{(2
7853:Loncastuximab tesirine
7582:Trastuzumab deruxtecan
6949:Interleukin-6 receptor
6375:Complement component 5
6012:Clinical trial number
4756:10.1038/sj.bjc.6602162
4560:10.1038/sj.onc.1209886
4335:10.1002/anie.200453764
3441:10.1681/ASN.2007111202
3267:10.1055/s-0036-1593383
2775:10.1186/2001-1326-1-29
2186:Lymphatic malformation
2181:Lymphatic malformation
2116:Topical administration
1970:
1822:(ORF's) designated as
1799:
1499:Impaired wound healing
1489:calcineurin inhibitors
1415:Diabetes-like symptoms
1276:deep venous thrombosis
1268:Venous thromboembolism
1132:Vascular malformations
1124:, under the tradename
1101:Coronary stent coating
993:calcineurin inhibitors
915:properties due to its
890:It is produced by the
9951:Anti-aging substances
8956:6,7-Dimethylesculetin
7928:Sacituzumab govitecan
7868:Moxetumomab pasudotox
7838:Inotuzumab ozogamicin
7741:Gemtuzumab ozogamicin
7577:Trastuzumab emtansine
7518:monoclonal antibodies
7502:antineoplastic agents
5662:Journal of Immunology
5471:Physiological Reviews
5016:10.1093/gerona/glw090
4874:Nature Reviews Cancer
4503:Journal of Immunology
4054:10.1056/NEJMoa1204166
2991:(FDA). 11 June 2009.
2881:Aadi Bioscience, Inc.
2423:. 17 September 2018.
1965:
1919:Claisen condensations
1797:
1586:FK-binding protein 12
1559:calcineurin inhibitor
1557:, sirolimus is not a
1122:Johnson & Johnson
1105:Further information:
1016:mycophenolate mofetil
1008:calcineurin inhibitor
860:transplants. It is a
9543:Hypericum perforatum
9532:Hetacillin potassium
7783:Belantamab mafodotin
5172:Janin A (May 2023).
5106:. 11 November 2020.
4962:"What is rapamycin?"
4868:Novak K (May 2004).
4635:(5): 211. May 2005.
2809:Drug Discovery Today
2073:Effects on longevity
2004:mantle cell lymphoma
1927:acyl carrier protein
1382:basal cell carcinoma
1327:lactic dehydrogenase
1176:hypertriglyceridemia
1172:hypercholesterolemia
9991:Ophthalmology drugs
9372:Cyproterone acetate
9272:Amlodipine besylate
8636:Denileukin diftitox
8298:(ALK, ROS1, NTRK),
7903:Polatuzumab vedotin
7893:Oportuzumab monatox
5778:10.1038/nm0996-1028
5379:2020CBI...33109282H
5229:10.1038/nature11861
5221:2013Natur.493..338J
5178:Wall Street Journal
4809:10.1038/nature02369
4801:2004Natur.428..332W
4642:10.1038/ncponc0156x
4279:1995PNAS...92.7839S
4100:1991Sci...253..905H
3384:2012Sci...335.1638L
3378:(6076): 1638–1643.
3115:10.1056/NEJMp068234
2693:10.1155/2009/701464
2390:. 28 January 2021.
2226:veterinary medicine
2011:combination therapy
1820:open reading frames
1713:polyketide synthase
832:among others, is a
754:Solubility in water
25:
16:Pharmaceutical drug
9956:Immunosuppressants
9845:Thonzonium bromide
9600:Methylprednisolone
9401:prasterone sulfate
8322:(ROS1, TRK, ALK),
7828:Enfortumab vedotin
7306:Diroximel fumarate
6979:IL-2 receptor/CD25
6407:Certolizumab pegol
6060:Immunosuppressants
6020:ClinicalTrials.gov
5068:10.1111/acel.13269
3490:10.1111/acel.12405
3147:on 17 January 2021
2951:. Momentum Press.
2229:teaching hospitals
2143:cell proliferation
1971:
1800:
1272:pulmonary embolism
1151:tuberous sclerosis
1107:Drug-eluting stent
971:tuberous sclerosis
881:drug-eluting stent
65:Rapamycin, ABI-009
21:
9916:
9915:
9550:Indinavir sulfate
9257:Alpha-Lipoic acid
9232:Δ-Androstenedione
9222:Δ-Androstenedione
8895:
8894:
8578:
8577:
7986:
7985:
7968:Tisotumab vedotin
7464:
7463:
7311:Efgartigimod alfa
7301:Dimethyl fumarate
7229:
7228:
7157:
7156:
7130:
7129:
6335:
6334:
6261:
6260:
6102:Mycophenolic acid
5841:. 28 March 2022.
5724:10.1111/ajt.16505
5668:(11): 5355–5365.
5624:10.1111/bcp.13022
5215:(7432): 338–345.
5137:(268): 268ra179.
4845:. 17 March 2004.
4795:(6980): 332–337.
4711:(16): 7052–7058.
4554:(48): 6436–6446.
4440:10.1021/ja0587603
4434:(11): 3838–3847.
4364:(19): 3565–3568.
4329:(19): 2551–2553.
4323:Angewandte Chemie
4273:(17): 7839–7843.
4094:(5022): 905–909.
3970:(13): 1750–1756.
3731:(12): 1659–1661.
3538:10.1159/000087945
3304:10.1111/jdv.12665
3109:(19): 1949–1952.
3020:JAMA Network Open
2958:978-1-60650-250-1
2919:978-1-118-35446-9
2163:endothelial cells
2147:viral replication
2135:immunosuppressive
1911:shikimate pathway
1874:chain termination
1814:The biosynthetic
1686:
1685:
1412:
1411:
1218:, dizziness, and
913:antiproliferative
854:immunosuppressant
852:(PEComa). It has
819:
818:
743:Interactive image
633:CompTox Dashboard
424:)-1--2-propanyl}-
270:
255:
149:
116:
99:
82:
10003:
9996:Chemical biology
9933:
9932:
9931:
9924:
9835:Thiamylal sodium
9570:γ-linolenic acid
9566:α-Linolenic acid
9564:Linolenic acid:
9555:Lasalocid sodium
9545:(St John's wort)
9437:Docusate calcium
9367:Cyclophosphamide
9242:Allopregnanediol
9227:Δ-Androstenediol
9202:
9198:
9156:Ethinylestradiol
9006:Cyclophosphamide
8946:
8942:
8922:
8915:
8908:
8899:
8898:
8609:peptide against
8182:(AXL, ALK, LTK))
7998:
7997:
7808:Dinutuximab beta
7524:
7523:
7491:
7484:
7477:
7468:
7467:
7107:Telimomab aritox
7010:Zolimomab aritox
6831:CD62L/L-selectin
6569:Immunoglobulin E
6362:
6361:
6353:
6352:
6344:
6343:
6272:
6271:
6078:
6077:
6049:
6042:
6035:
6026:
6025:
6001:
5984:(5): 1321–1333.
5972:
5954:
5929:
5882:
5878:
5876:
5874:
5854:
5852:
5850:
5830:
5828:
5826:
5817:. 29 July 2022.
5804:
5798:
5797:
5772:(9): 1028–1032.
5761:
5755:
5754:
5736:
5726:
5717:(8): 2662–2674.
5702:
5696:
5695:
5677:
5653:
5647:
5646:
5636:
5626:
5617:(5): 1171–1179.
5602:
5596:
5595:
5585:
5568:(8): 3801–3810.
5553:
5547:
5546:
5536:
5504:
5495:
5494:
5477:(4): 1381–1478.
5466:
5460:
5459:
5449:
5439:
5415:
5409:
5408:
5398:
5358:
5349:
5348:
5338:
5306:
5300:
5299:
5289:
5257:
5251:
5250:
5240:
5200:
5194:
5193:
5191:
5189:
5169:
5163:
5162:
5126:
5120:
5119:
5117:
5115:
5096:
5090:
5089:
5079:
5047:
5041:
5040:
5027:
4995:
4982:
4981:
4979:
4977:
4957:
4951:
4950:
4940:
4930:
4906:
4900:
4899:
4889:
4865:
4859:
4858:
4856:
4854:
4835:
4829:
4828:
4784:
4778:
4777:
4767:
4750:(8): 1420–1424.
4735:
4729:
4728:
4700:
4694:
4693:
4691:
4689:
4669:
4663:
4662:
4644:
4621:
4615:
4614:
4586:
4580:
4579:
4543:
4537:
4536:
4526:
4509:(7): 3080–3087.
4494:
4488:
4487:
4458:
4452:
4451:
4423:
4417:
4416:
4405:10.1039/b804602f
4388:
4382:
4381:
4370:10.1039/b608813a
4353:
4347:
4346:
4317:
4311:
4310:
4300:
4290:
4258:
4247:
4246:
4209:
4203:
4202:
4174:
4168:
4167:
4139:
4128:
4127:
4083:
4077:
4076:
4066:
4056:
4032:
4026:
4025:
4008:(8): 3053–3054.
3996:
3990:
3989:
3979:
3955:
3949:
3948:
3920:
3914:
3913:
3895:
3867:
3861:
3860:
3832:
3826:
3825:
3808:(9): 1171–1174.
3797:
3791:
3790:
3762:
3756:
3755:
3753:
3751:
3745:
3725:Respiratory Care
3722:
3713:
3707:
3706:
3688:
3679:(8): 1215–1220.
3664:
3658:
3657:
3655:
3653:
3628:(7): 2792–2797.
3613:
3607:
3606:
3588:
3564:
3558:
3557:
3521:
3512:
3511:
3501:
3469:
3463:
3462:
3452:
3435:(7): 1411–1418.
3420:
3414:
3413:
3403:
3363:
3354:
3353:
3351:
3349:
3340:. 7 April 2022.
3330:
3324:
3323:
3286:
3280:
3279:
3269:
3245:
3239:
3238:
3228:
3204:
3198:
3197:
3187:
3163:
3157:
3156:
3154:
3152:
3143:. Archived from
3133:
3127:
3126:
3098:
3092:
3091:
3089:
3087:
3067:
3056:
3055:
3045:
3035:
3011:
3005:
3004:
3002:
3000:
2981:
2975:
2974:
2972:
2970:
2942:
2936:
2935:
2933:
2931:
2903:
2897:
2896:
2894:
2892:
2873:
2867:
2866:
2864:
2862:
2839:
2833:
2832:
2804:
2798:
2797:
2787:
2777:
2753:
2747:
2746:
2744:
2742:
2722:
2716:
2715:
2705:
2695:
2671:
2654:
2653:
2651:
2649:
2644:on 27 April 2003
2640:. Archived from
2630:
2621:
2620:
2610:
2586:
2577:
2576:
2548:
2542:
2541:
2539:
2537:
2526:PubChem Compound
2518:
2507:
2506:
2504:
2502:
2481:Buck ML (2006).
2478:
2472:
2470:
2468:
2466:
2448:
2437:
2436:
2434:
2432:
2413:
2404:
2403:
2401:
2399:
2380:
2374:
2373:
2371:
2369:
2350:
2337:
2336:
2334:
2332:
2313:
2280:
2279:
2277:
2275:
2265:nctr-crs.fda.gov
2257:
2039:cyclophosphamide
1984:Kaposi's sarcoma
1913:. Note that the
1808:cytochrome P-450
1784:
1765:
1745:
1681:
1678:
1660:
1653:
1606:Pharmacokinetics
1543:Pharmacodynamics
1280:rapid heart rate
1234:Adverse effects
1228:
1227:
1200:thrombocytopenia
1168:peripheral edema
1120:, a division of
1085:renal transplant
1020:thrombocytopenia
969:associated with
824:, also known as
815:
814:
745:
725:
710:
707:
701:
695:
678:
667:
656:
655:
641:
639:
623:
617:
596:
576:
556:
536:
516:
496:
476:
466:
465:
451:
323:
268:
265:
260:
253:
250:
228:
218:
208:
198:
147:
144:
126:
115:
112:
109:
98:
95:
92:
81:
78:
42:
33:
26:
24:
20:
10011:
10010:
10006:
10005:
10004:
10002:
10001:
10000:
9941:
9940:
9939:
9929:
9927:
9919:
9917:
9912:
9894:
9795:Suberoylanilide
9512:Fluorometholone
9407:Dibunate sodium
9287:Aurothioglucose
9200:
9190:
9126:3,17β-Estradiol
8944:
8934:
8926:
8896:
8891:
8745:Pi3K inhibitors
8643:mTOR inhibitors
8574:
8355:
8326:(VEGFR, FGFR),
7982:
7746:
7627:
7587:
7509:
7495:
7465:
7460:
7406:Rozanolixizumab
7291:Deucravacitinib
7225:
7153:
7126:
7015:
6664:
6658:
6366:
6331:
6288:
6267:
6257:
6215:
6155:
6146:
6082:Antimetabolites
6073:
6067:
6053:
6009:
6004:
5910:10.1038/nrd3531
5904:(11): 868–880.
5891:
5889:Further reading
5886:
5885:
5881:
5872:
5870:
5857:
5848:
5846:
5833:
5824:
5822:
5809:
5805:
5801:
5766:Nature Medicine
5762:
5758:
5703:
5699:
5654:
5650:
5603:
5599:
5554:
5550:
5505:
5498:
5467:
5463:
5416:
5412:
5359:
5352:
5307:
5303:
5278:10.1038/nri3901
5272:(10): 599–614.
5258:
5254:
5201:
5197:
5187:
5185:
5170:
5166:
5127:
5123:
5113:
5111:
5098:
5097:
5093:
5048:
5044:
4996:
4985:
4975:
4973:
4958:
4954:
4907:
4903:
4887:10.1038/nrc1349
4866:
4862:
4852:
4850:
4837:
4836:
4832:
4785:
4781:
4736:
4732:
4705:Cancer Research
4701:
4697:
4687:
4685:
4670:
4666:
4623:
4622:
4618:
4587:
4583:
4544:
4540:
4495:
4491:
4459:
4455:
4424:
4420:
4389:
4385:
4354:
4350:
4318:
4314:
4259:
4250:
4210:
4206:
4175:
4171:
4140:
4131:
4084:
4080:
4033:
4029:
3997:
3993:
3956:
3952:
3921:
3917:
3868:
3864:
3833:
3829:
3798:
3794:
3763:
3759:
3749:
3747:
3743:
3720:
3714:
3710:
3673:Transplantation
3665:
3661:
3651:
3649:
3614:
3610:
3573:Transplantation
3565:
3561:
3522:
3515:
3470:
3466:
3421:
3417:
3364:
3357:
3347:
3345:
3332:
3331:
3327:
3287:
3283:
3246:
3242:
3205:
3201:
3164:
3160:
3150:
3148:
3135:
3134:
3130:
3099:
3095:
3085:
3083:
3068:
3059:
3026:(8): e1910297.
3012:
3008:
2998:
2996:
2983:
2982:
2978:
2968:
2966:
2959:
2943:
2939:
2929:
2927:
2920:
2904:
2900:
2890:
2888:
2875:
2874:
2870:
2860:
2858:
2841:
2840:
2836:
2815:(10): 688–691.
2805:
2801:
2754:
2750:
2740:
2738:
2723:
2719:
2672:
2657:
2647:
2645:
2632:
2631:
2624:
2601:(10): 721–726.
2587:
2580:
2549:
2545:
2535:
2533:
2520:
2519:
2510:
2500:
2498:
2479:
2475:
2464:
2462:
2450:
2449:
2440:
2430:
2428:
2417:"Rapamune EPAR"
2415:
2414:
2407:
2397:
2395:
2382:
2381:
2377:
2367:
2365:
2352:
2351:
2340:
2330:
2328:
2315:
2314:
2283:
2273:
2271:
2259:
2258:
2254:
2249:
2222:
2220:Veterinary uses
2210:
2194:
2183:
2171:
2155:
2153:Atherosclerosis
2133:insofar as its
2127:
2118:
2075:
2063:angiomyolipomas
2055:
2033:drugs, such as
1988:mTOR inhibitors
1976:
1960:
1792:
1791:
1790:
1789:
1788:
1785:
1777:
1776:
1766:
1755:
1754:
1753:
1751:
1746:
1705:
1690:natural product
1688:Sirolimus is a
1682:
1676:
1673:
1666:needs expansion
1651:
1643:pharmacokinetic
1608:
1551:
1549:mTOR inhibitors
1545:
1540:
1513:
1505:body mass index
1501:
1473:
1465:
1445:
1417:
1342:Musculoskeletal
1239:Body as a whole
1212:nasopharyngitis
1163:
1161:Adverse effects
1143:
1134:
1113:coronary stents
1109:
1103:
1060:clinical trials
1029:
989:
983:Organ rejection
979:
933:
838:coronary stents
810:
808:
803:
800:
795:
790:
789:
778:
775:
770:
769:
748:
723:
713:
704:
698:
659:
635:
627:
599:
579:
559:
539:
519:
499:
479:
462:
454:
434:
431:
429:
427:
425:
407:
354:
353:
321:
298:Protein binding
288:Bioavailability
280:Pharmacokinetic
274:
258:
232:
162:
155:
136:
129:
17:
12:
11:
5:
10009:
9999:
9998:
9993:
9988:
9983:
9978:
9973:
9968:
9963:
9958:
9953:
9938:
9937:
9914:
9913:
9911:
9910:
9903:
9899:
9896:
9895:
9893:
9892:
9887:
9878:
9877:
9872:
9867:
9862:
9860:Troleandomycin
9857:
9852:
9847:
9842:
9837:
9832:
9827:
9822:
9817:
9812:
9807:
9802:
9797:
9792:
9787:
9782:
9780:Spironolactone
9777:
9772:
9767:
9762:
9757:
9752:
9747:
9742:
9737:
9732:
9727:
9722:
9717:
9712:
9707:
9702:
9697:
9692:
9687:
9682:
9677:
9672:
9667:
9662:
9657:
9652:
9650:Norelgestromin
9647:
9642:
9637:
9632:
9627:
9622:
9617:
9612:
9607:
9602:
9597:
9592:
9587:
9582:
9577:
9572:
9562:
9557:
9552:
9547:
9539:
9534:
9529:
9524:
9519:
9514:
9509:
9507:Flucloxacillin
9504:
9499:
9494:
9489:
9484:
9479:
9474:
9469:
9464:
9459:
9454:
9449:
9444:
9439:
9434:
9429:
9424:
9419:
9414:
9409:
9404:
9394:
9384:
9379:
9374:
9369:
9364:
9362:Corticosterone
9359:
9354:
9349:
9344:
9339:
9334:
9329:
9327:Chlorpromazine
9324:
9319:
9314:
9309:
9304:
9299:
9294:
9289:
9284:
9279:
9274:
9269:
9264:
9259:
9254:
9249:
9244:
9239:
9234:
9229:
9224:
9219:
9214:
9205:
9203:
9192:
9191:
9189:
9188:
9183:
9178:
9173:
9168:
9163:
9158:
9153:
9148:
9146:17-Androstanol
9143:
9141:3β-Androstanol
9138:
9136:3α-Androstenol
9133:
9131:3α-Androstanol
9128:
9119:
9118:
9113:
9108:
9103:
9098:
9093:
9088:
9083:
9078:
9073:
9068:
9063:
9058:
9053:
9048:
9043:
9038:
9033:
9028:
9023:
9013:
9008:
9003:
8998:
8993:
8988:
8986:Chlorpromazine
8983:
8978:
8973:
8968:
8963:
8958:
8949:
8947:
8936:
8935:
8925:
8924:
8917:
8910:
8902:
8893:
8892:
8890:
8889:
8884:
8879:
8874:
8869:
8864:
8859:
8854:
8849:
8844:
8839:
8834:
8829:
8824:
8819:
8814:
8809:
8804:
8799:
8794:
8789:
8784:
8779:
8774:
8773:
8772:
8767:
8762:
8757:
8752:
8742:
8741:
8740:
8735:
8722:
8721:
8720:
8715:
8710:
8705:
8700:
8692:CDK inhibitors
8688:
8687:
8686:
8681:
8676:
8663:
8662:
8661:
8656:
8651:
8639:
8623:
8603:
8591:fusion protein
8586:
8584:
8580:
8579:
8576:
8575:
8573:
8572:
8571:
8570:
8565:
8560:
8555:
8550:
8537:
8536:
8535:
8534:
8529:
8524:
8507:
8506:
8505:
8504:
8499:
8494:
8489:
8476:
8475:
8474:
8473:
8468:
8463:
8458:
8453:
8448:
8443:
8430:
8429:
8423:
8411:
8410:
8409:
8408:
8403:
8398:
8393:
8388:
8383:
8378:
8365:
8363:
8357:
8356:
8354:
8353:
8332:
8331:
8330:(VEGFR, EGFR).
8286:
8285:
8284:
8283:
8278:
8273:
8260:
8259:
8258:
8257:
8252:
8247:
8242:
8237:
8232:
8227:
8222:
8217:
8212:
8207:
8202:
8197:
8184:
8183:
8167:
8161:
8156:
8151:
8146:
8141:
8136:
8131:
8111:
8110:
8109:
8108:
8103:
8098:
8088:HER1/EGFR and
8084:
8083:
8077:
8072:
8067:
8062:
8057:
8052:
8047:
8042:
8037:
8032:
8027:
8022:
8006:
8004:
7995:
7988:
7987:
7984:
7983:
7981:
7980:
7975:
7970:
7965:
7960:
7955:
7950:
7945:
7940:
7935:
7930:
7925:
7920:
7915:
7910:
7905:
7900:
7895:
7890:
7885:
7880:
7875:
7870:
7865:
7860:
7855:
7850:
7845:
7840:
7835:
7830:
7825:
7820:
7815:
7810:
7805:
7800:
7795:
7790:
7785:
7780:
7775:
7770:
7767:+hyaluronidase
7760:
7754:
7752:
7748:
7747:
7745:
7744:
7727:
7726:
7700:
7695:
7690:
7685:
7680:
7675:
7641:
7639:
7629:
7628:
7626:
7625:
7613:
7607:
7595:
7593:
7589:
7588:
7586:
7585:
7579:
7574:
7571:+hyaluronidase
7554:
7548:
7532:
7530:
7521:
7511:
7510:
7494:
7493:
7486:
7479:
7471:
7462:
7461:
7459:
7458:
7453:
7448:
7443:
7438:
7433:
7428:
7423:
7418:
7413:
7408:
7403:
7398:
7393:
7388:
7383:
7378:
7373:
7368:
7363:
7358:
7353:
7348:
7343:
7338:
7333:
7328:
7323:
7318:
7315:+hyaluronidase
7308:
7303:
7298:
7296:Deuruxolitinib
7293:
7288:
7283:
7278:
7273:
7268:
7263:
7258:
7253:
7248:
7243:
7237:
7235:
7231:
7230:
7227:
7226:
7224:
7223:
7218:
7213:
7208:
7207:
7206:
7201:
7189:
7188:
7187:
7182:
7169:
7167:
7159:
7158:
7155:
7154:
7152:
7151:
7146:
7140:
7138:
7132:
7131:
7128:
7127:
7125:
7124:
7119:
7114:
7109:
7104:
7099:
7094:
7089:
7084:
7079:
7074:
7069:
7064:
7059:
7054:
7049:
7044:
7039:
7034:
7029:
7023:
7021:
7017:
7016:
7014:
7013:
7000:
6999:
6998:
6997:
6992:
6987:
6974:
6973:
6972:
6971:
6959:
6958:
6957:
6945:
6944:
6943:
6938:
6926:
6925:
6924:
6919:
6914:
6902:
6901:
6900:
6889:
6888:
6887:
6886:
6881:
6869:
6868:
6867:
6855:
6854:
6853:
6841:
6840:
6839:
6827:
6826:
6825:
6820:
6808:
6807:
6806:
6801:
6789:
6788:
6787:
6782:
6777:
6772:
6769:+hyaluronidase
6762:
6750:
6749:
6748:
6736:
6735:
6734:
6722:
6721:
6720:
6715:
6710:
6698:
6697:
6696:
6691:
6686:
6681:
6668:
6666:
6660:
6659:
6657:
6656:
6655:
6654:
6641:
6640:
6639:
6638:
6633:
6612:
6611:
6610:
6609:
6596:
6595:
6594:
6593:
6580:
6579:
6578:
6577:
6564:
6563:
6562:
6561:
6548:
6547:
6546:
6545:
6540:
6535:
6530:
6525:
6520:
6515:
6510:
6505:
6500:
6495:
6490:
6485:
6480:
6475:
6470:
6465:
6460:
6455:
6450:
6445:
6440:
6427:
6426:
6425:
6424:
6419:
6414:
6409:
6404:
6399:
6386:
6385:
6384:
6383:
6370:
6368:
6359:
6350:
6341:
6337:
6336:
6333:
6332:
6330:
6329:
6324:
6319:
6314:
6309:
6304:
6298:
6296:
6290:
6289:
6287:
6286:
6280:
6278:
6269:
6263:
6262:
6259:
6258:
6256:
6255:
6254:
6253:
6245:PDE4 inhibitor
6241:
6236:
6231:
6225:
6223:
6217:
6216:
6214:
6213:
6208:
6202:
6201:
6200:
6199:
6194:
6189:
6184:
6163:
6161:
6148:
6147:
6145:
6144:
6143:
6142:
6129:
6128:
6127:
6126:
6121:
6107:
6106:
6105:
6104:
6099:
6086:
6084:
6075:
6069:
6068:
6052:
6051:
6044:
6037:
6029:
6023:
6022:
6008:
6007:External links
6005:
6003:
6002:
5973:
5945:(1): 318–327.
5930:
5892:
5890:
5887:
5884:
5883:
5880:
5879:
5855:
5831:
5806:
5799:
5756:
5697:
5648:
5597:
5548:
5496:
5461:
5410:
5350:
5321:(6): 861–869.
5301:
5252:
5195:
5164:
5121:
5091:
5062:(11): e13269.
5042:
5010:(7): 841–849.
4983:
4952:
4901:
4860:
4830:
4779:
4730:
4695:
4678:Med Page Today
4664:
4616:
4581:
4538:
4489:
4453:
4418:
4399:(5): 602–609.
4383:
4348:
4312:
4248:
4221:(3): 346–350.
4204:
4169:
4150:(4): 416–428.
4129:
4078:
4047:(4): 329–339.
4027:
3991:
3950:
3915:
3878:(8): 499–510.
3862:
3843:(2): 210–213.
3827:
3792:
3773:(3): 296–298.
3757:
3708:
3659:
3608:
3579:(5): 787–790.
3559:
3532:(3): 367–374.
3513:
3464:
3415:
3355:
3325:
3281:
3240:
3199:
3178:(4): 756–763.
3158:
3128:
3093:
3057:
3006:
2976:
2957:
2937:
2918:
2898:
2868:
2834:
2799:
2748:
2717:
2655:
2622:
2578:
2559:(1–2): 25–29.
2543:
2508:
2473:
2438:
2405:
2375:
2338:
2281:
2251:
2250:
2248:
2245:
2233:clinical study
2221:
2218:
2209:
2206:
2193:
2190:
2182:
2179:
2170:
2167:
2154:
2151:
2139:cytokine storm
2126:
2123:
2117:
2114:
2074:
2071:
2054:
2051:
1975:
1972:
1959:
1956:
1950:by MTases and
1855:pipecolic acid
1786:
1779:
1778:
1767:
1760:
1759:
1758:
1757:
1756:
1748:
1747:
1740:
1739:
1738:
1723:of the linear
1704:
1701:
1684:
1683:
1663:
1661:
1650:
1647:
1619:P-glycoprotein
1607:
1604:
1544:
1541:
1539:
1536:
1524:P-glycoprotein
1512:
1509:
1500:
1497:
1472:
1469:
1464:
1461:
1444:
1441:
1416:
1413:
1410:
1409:
1394:Pyelonephritis
1391:
1385:
1384:
1371:
1367:
1366:
1357:
1351:
1350:
1344:
1338:
1337:
1323:
1319:
1318:
1305:
1295:
1294:
1289:
1283:
1282:
1265:
1263:Cardiovascular
1259:
1258:
1255:herpes simplex
1240:
1236:
1235:
1232:
1162:
1159:
1142:
1139:
1133:
1130:
1102:
1099:
1053:growth factors
1028:
1025:
997:kidney failure
978:
975:
932:
929:
817:
816:
805:
804:
802:
801:
798:
796:
793:
785:
784:
783:
780:
779:
777:
776:
773:
765:
764:
763:
760:
759:
756:
750:
749:
747:
746:
738:
736:
728:
727:
721:
715:
714:
711:
702:
696:
691:
685:
684:
680:
679:
669:
661:
660:
658:
657:
644:
642:
629:
628:
626:
625:
609:
607:
601:
600:
598:
597:
589:
587:
581:
580:
578:
577:
569:
567:
561:
560:
558:
557:
549:
547:
541:
540:
538:
537:
529:
527:
521:
520:
518:
517:
509:
507:
501:
500:
498:
497:
489:
487:
481:
480:
478:
477:
469:
467:
456:
455:
453:
452:
444:
442:
436:
435:
433:
432:
357:
349:
348:
347:
344:
343:
339:
338:
335:
329:
328:
325:
316:
315:
310:
304:
303:
300:
294:
293:
290:
284:
283:
276:
275:
273:
272:
263:
247:
245:
239:
238:
234:
233:
231:
230:
187:
185:
179:
178:
165:
163:administration
157:
156:
154:
153:
151:
141:
139:
131:
130:
128:
127:
110:
93:
75:
73:
67:
66:
63:
59:
58:
55:
49:
48:
44:
43:
35:
34:
15:
9:
6:
4:
3:
2:
10008:
9997:
9994:
9992:
9989:
9987:
9984:
9982:
9979:
9977:
9974:
9972:
9969:
9967:
9964:
9962:
9959:
9957:
9954:
9952:
9949:
9948:
9946:
9936:
9926:
9925:
9922:
9909:
9908:
9904:
9901:
9900:
9897:
9891:
9888:
9886:
9883:
9880:
9879:
9876:
9873:
9871:
9868:
9866:
9863:
9861:
9858:
9856:
9853:
9851:
9848:
9846:
9843:
9841:
9838:
9836:
9833:
9831:
9828:
9826:
9823:
9821:
9818:
9816:
9813:
9811:
9808:
9806:
9803:
9801:
9800:Sulfisoxazole
9798:
9796:
9793:
9791:
9788:
9786:
9783:
9781:
9778:
9776:
9773:
9771:
9768:
9766:
9763:
9761:
9758:
9756:
9753:
9751:
9748:
9746:
9743:
9741:
9738:
9736:
9733:
9731:
9728:
9726:
9723:
9721:
9718:
9716:
9713:
9711:
9708:
9706:
9703:
9701:
9698:
9696:
9693:
9691:
9688:
9686:
9683:
9681:
9678:
9676:
9675:Phenobarbital
9673:
9671:
9668:
9666:
9663:
9661:
9658:
9656:
9653:
9651:
9648:
9646:
9643:
9641:
9638:
9636:
9633:
9631:
9628:
9626:
9623:
9621:
9618:
9616:
9613:
9611:
9608:
9606:
9603:
9601:
9598:
9596:
9593:
9591:
9588:
9586:
9583:
9581:
9578:
9576:
9573:
9571:
9567:
9563:
9561:
9560:Levothyroxine
9558:
9556:
9553:
9551:
9548:
9546:
9544:
9540:
9538:
9535:
9533:
9530:
9528:
9525:
9523:
9522:Guggulsterone
9520:
9518:
9515:
9513:
9510:
9508:
9505:
9503:
9500:
9498:
9495:
9493:
9490:
9488:
9485:
9483:
9480:
9478:
9475:
9473:
9470:
9468:
9465:
9463:
9460:
9458:
9455:
9453:
9450:
9448:
9445:
9443:
9440:
9438:
9435:
9433:
9430:
9428:
9425:
9423:
9420:
9418:
9417:Dicloxacillin
9415:
9413:
9410:
9408:
9405:
9402:
9398:
9395:
9392:
9388:
9385:
9383:
9382:Dexamethasone
9380:
9378:
9375:
9373:
9370:
9368:
9365:
9363:
9360:
9358:
9355:
9353:
9350:
9348:
9345:
9343:
9340:
9338:
9335:
9333:
9330:
9328:
9325:
9323:
9320:
9318:
9317:Cephaloridine
9315:
9313:
9310:
9308:
9305:
9303:
9300:
9298:
9295:
9293:
9290:
9288:
9285:
9283:
9280:
9278:
9275:
9273:
9270:
9268:
9265:
9263:
9260:
9258:
9255:
9253:
9250:
9248:
9245:
9243:
9240:
9238:
9235:
9233:
9230:
9228:
9225:
9223:
9220:
9218:
9215:
9213:
9210:
9207:
9206:
9204:
9199:
9193:
9187:
9184:
9182:
9179:
9177:
9174:
9172:
9169:
9167:
9164:
9162:
9159:
9157:
9154:
9152:
9149:
9147:
9144:
9142:
9139:
9137:
9134:
9132:
9129:
9127:
9124:
9121:
9120:
9117:
9116:Valproic acid
9114:
9112:
9109:
9107:
9104:
9102:
9099:
9097:
9094:
9092:
9089:
9087:
9084:
9082:
9079:
9077:
9076:Phenobarbital
9074:
9072:
9069:
9067:
9064:
9062:
9059:
9057:
9054:
9052:
9049:
9047:
9044:
9042:
9039:
9037:
9034:
9032:
9029:
9027:
9024:
9021:
9017:
9014:
9012:
9009:
9007:
9004:
9002:
8999:
8997:
8994:
8992:
8989:
8987:
8984:
8982:
8979:
8977:
8976:Carbamazepine
8974:
8972:
8969:
8967:
8964:
8962:
8959:
8957:
8954:
8951:
8950:
8948:
8943:
8937:
8933:
8930:
8923:
8918:
8916:
8911:
8909:
8904:
8903:
8900:
8888:
8885:
8883:
8880:
8878:
8875:
8873:
8870:
8868:
8865:
8863:
8860:
8858:
8855:
8853:
8850:
8848:
8845:
8843:
8840:
8838:
8835:
8833:
8830:
8828:
8825:
8823:
8820:
8818:
8815:
8813:
8810:
8808:
8805:
8803:
8802:Larotrectinib
8800:
8798:
8795:
8793:
8790:
8788:
8785:
8783:
8780:
8778:
8775:
8771:
8768:
8766:
8763:
8761:
8758:
8756:
8753:
8751:
8748:
8747:
8746:
8743:
8739:
8736:
8734:
8731:
8730:
8729:
8727:
8723:
8719:
8716:
8714:
8711:
8709:
8706:
8704:
8701:
8699:
8696:
8695:
8694:
8693:
8689:
8685:
8682:
8680:
8677:
8675:
8672:
8671:
8670:
8668:
8664:
8660:
8657:
8655:
8654:Ridaforolimus
8652:
8650:
8647:
8646:
8645:
8644:
8640:
8637:
8633:
8632:
8628:
8624:
8621:
8617:
8616:
8612:
8608:
8604:
8601:
8597:
8596:
8592:
8588:
8587:
8585:
8581:
8569:
8566:
8564:
8563:Pirtobrutinib
8561:
8559:
8558:Orelabrutinib
8556:
8554:
8551:
8549:
8548:Acalabrutinib
8546:
8545:
8544:
8543:
8539:
8538:
8533:
8530:
8528:
8525:
8523:
8520:
8519:
8518:
8517:
8513:
8509:
8508:
8503:
8500:
8498:
8495:
8493:
8490:
8488:
8485:
8484:
8483:
8482:
8478:
8477:
8472:
8469:
8467:
8464:
8462:
8459:
8457:
8454:
8452:
8449:
8447:
8444:
8442:
8439:
8438:
8437:
8436:
8432:
8431:
8427:
8424:
8422:
8418:
8417:
8413:
8412:
8407:
8404:
8402:
8399:
8397:
8394:
8392:
8389:
8387:
8384:
8382:
8379:
8377:
8374:
8373:
8372:
8371:
8367:
8366:
8364:
8362:
8358:
8351:
8347:
8343:
8340:
8338:
8334:
8333:
8329:
8325:
8324:Selpercatinib
8321:
8320:Repotrectinib
8317:
8313:
8309:
8308:Larotrectinib
8305:
8301:
8297:
8294:
8292:
8288:
8287:
8282:
8279:
8277:
8274:
8272:
8269:
8268:
8267:
8266:
8262:
8261:
8256:
8253:
8251:
8248:
8246:
8243:
8241:
8238:
8236:
8233:
8231:
8228:
8226:
8223:
8221:
8218:
8216:
8213:
8211:
8208:
8206:
8203:
8201:
8198:
8196:
8193:
8192:
8191:
8190:
8186:
8185:
8181:
8177:
8173:
8172:
8168:
8165:
8162:
8160:
8157:
8155:
8152:
8150:
8147:
8145:
8142:
8140:
8137:
8135:
8132:
8130:
8126:
8125:
8121:
8116:
8115:RTK class III
8113:
8112:
8107:
8104:
8102:
8099:
8097:
8094:
8093:
8092:
8091:
8086:
8085:
8081:
8078:
8076:
8073:
8071:
8068:
8066:
8063:
8061:
8058:
8056:
8053:
8051:
8048:
8046:
8043:
8041:
8038:
8036:
8033:
8031:
8028:
8026:
8023:
8021:
8017:
8016:
8011:
8008:
8007:
8005:
8003:
7999:
7996:
7993:
7989:
7979:
7976:
7974:
7971:
7969:
7966:
7964:
7961:
7959:
7956:
7954:
7951:
7949:
7946:
7944:
7941:
7939:
7936:
7934:
7931:
7929:
7926:
7924:
7921:
7919:
7916:
7914:
7911:
7909:
7906:
7904:
7901:
7899:
7898:Pembrolizumab
7896:
7894:
7891:
7889:
7886:
7884:
7881:
7879:
7876:
7874:
7871:
7869:
7866:
7864:
7863:Mogamulizumab
7861:
7859:
7856:
7854:
7851:
7849:
7846:
7844:
7841:
7839:
7836:
7834:
7831:
7829:
7826:
7824:
7821:
7819:
7816:
7814:
7811:
7809:
7806:
7804:
7801:
7799:
7796:
7794:
7791:
7789:
7786:
7784:
7781:
7779:
7776:
7774:
7771:
7768:
7764:
7761:
7759:
7756:
7755:
7753:
7749:
7742:
7738:
7737:
7732:
7729:
7728:
7724:
7720:
7719:
7714:
7710:
7709:
7704:
7701:
7699:
7696:
7694:
7691:
7689:
7686:
7684:
7683:Mosunetuzumab
7681:
7679:
7676:
7674:
7670:
7669:
7664:
7663:Mosunetuzumab
7660:
7656:
7652:
7651:
7646:
7643:
7642:
7640:
7638:
7634:
7630:
7623:
7619:
7618:
7614:
7611:
7608:
7606:
7602:
7601:
7597:
7596:
7594:
7590:
7583:
7580:
7578:
7575:
7572:
7568:
7564:
7560:
7559:
7555:
7552:
7549:
7547:
7543:
7542:
7537:
7534:
7533:
7531:
7529:
7525:
7522:
7519:
7516:
7512:
7507:
7503:
7499:
7492:
7487:
7485:
7480:
7478:
7473:
7472:
7469:
7457:
7454:
7452:
7449:
7447:
7446:Tildrakizumab
7444:
7442:
7439:
7437:
7434:
7432:
7429:
7427:
7424:
7422:
7419:
7417:
7414:
7412:
7409:
7407:
7404:
7402:
7399:
7397:
7394:
7392:
7389:
7387:
7384:
7382:
7379:
7377:
7376:Pegcetacoplan
7374:
7372:
7369:
7367:
7364:
7362:
7359:
7357:
7354:
7352:
7349:
7347:
7344:
7342:
7339:
7337:
7334:
7332:
7329:
7327:
7324:
7322:
7319:
7316:
7312:
7309:
7307:
7304:
7302:
7299:
7297:
7294:
7292:
7289:
7287:
7286:Darvadstrocel
7284:
7282:
7279:
7277:
7274:
7272:
7269:
7267:
7264:
7262:
7259:
7257:
7254:
7252:
7249:
7247:
7244:
7242:
7239:
7238:
7236:
7232:
7222:
7219:
7217:
7214:
7212:
7209:
7205:
7202:
7200:
7197:
7196:
7195:
7194:
7193:TNF inhibitor
7190:
7186:
7183:
7181:
7178:
7177:
7176:
7175:
7171:
7170:
7168:
7165:
7160:
7150:
7147:
7145:
7142:
7141:
7139:
7137:
7133:
7123:
7120:
7118:
7115:
7113:
7110:
7108:
7105:
7103:
7100:
7098:
7095:
7093:
7090:
7088:
7085:
7083:
7080:
7078:
7075:
7073:
7070:
7068:
7065:
7063:
7060:
7058:
7055:
7053:
7050:
7048:
7045:
7043:
7040:
7038:
7035:
7033:
7030:
7028:
7025:
7024:
7022:
7018:
7011:
7007:
7006:
7002:
7001:
6996:
6993:
6991:
6988:
6986:
6983:
6982:
6981:
6980:
6976:
6975:
6970:
6967:
6966:
6965:
6964:
6960:
6956:
6953:
6952:
6951:
6950:
6946:
6942:
6939:
6937:
6934:
6933:
6932:
6931:
6927:
6923:
6920:
6918:
6915:
6913:
6910:
6909:
6908:
6907:
6903:
6899:
6896:
6895:
6894:
6891:
6890:
6885:
6882:
6880:
6877:
6876:
6875:
6874:
6870:
6866:
6863:
6862:
6861:
6860:
6859:CD147/Basigin
6856:
6852:
6849:
6848:
6847:
6846:
6842:
6838:
6835:
6834:
6833:
6832:
6828:
6824:
6821:
6819:
6816:
6815:
6814:
6813:
6809:
6805:
6802:
6800:
6797:
6796:
6795:
6794:
6790:
6786:
6783:
6781:
6778:
6776:
6773:
6770:
6766:
6763:
6761:
6758:
6757:
6756:
6755:
6751:
6747:
6744:
6743:
6742:
6741:
6737:
6733:
6730:
6729:
6728:
6727:
6723:
6719:
6716:
6714:
6711:
6709:
6706:
6705:
6704:
6703:
6699:
6695:
6692:
6690:
6687:
6685:
6682:
6680:
6679:Muromonab-CD3
6677:
6676:
6675:
6674:
6670:
6669:
6667:
6661:
6653:
6650:
6649:
6648:
6647:
6643:
6642:
6637:
6634:
6632:
6629:
6628:
6627:
6626:
6622:
6618:
6614:
6613:
6608:
6605:
6604:
6603:
6602:
6598:
6597:
6592:
6589:
6588:
6587:
6586:
6582:
6581:
6576:
6573:
6572:
6571:
6570:
6566:
6565:
6560:
6557:
6556:
6555:
6554:
6553:Interleukin 5
6550:
6549:
6544:
6541:
6539:
6536:
6534:
6533:Tildrakizumab
6531:
6529:
6526:
6524:
6521:
6519:
6516:
6514:
6511:
6509:
6506:
6504:
6501:
6499:
6496:
6494:
6491:
6489:
6486:
6484:
6481:
6479:
6476:
6474:
6471:
6469:
6466:
6464:
6461:
6459:
6456:
6454:
6451:
6449:
6446:
6444:
6441:
6439:
6436:
6435:
6434:
6433:
6429:
6428:
6423:
6420:
6418:
6415:
6413:
6410:
6408:
6405:
6403:
6400:
6398:
6395:
6394:
6393:
6392:
6388:
6387:
6382:
6379:
6378:
6377:
6376:
6372:
6371:
6369:
6367:(noncellular)
6363:
6360:
6358:
6354:
6351:
6349:
6345:
6342:
6340:Extracellular
6338:
6328:
6325:
6323:
6320:
6318:
6315:
6313:
6310:
6308:
6307:Ridaforolimus
6305:
6303:
6300:
6299:
6297:
6295:
6291:
6285:
6282:
6281:
6279:
6277:
6273:
6270:
6266:Intracellular
6264:
6252:
6249:
6248:
6247:
6246:
6242:
6240:
6237:
6235:
6232:
6230:
6227:
6226:
6224:
6222:
6218:
6212:
6209:
6207:
6204:
6203:
6198:
6195:
6193:
6190:
6188:
6185:
6183:
6180:
6179:
6178:
6177:
6173:
6169:
6165:
6164:
6162:
6159:
6153:
6149:
6141:
6138:
6137:
6136:
6135:
6131:
6130:
6125:
6124:Teriflunomide
6122:
6120:
6117:
6116:
6114:
6113:
6109:
6108:
6103:
6100:
6098:
6095:
6094:
6093:
6092:
6088:
6087:
6085:
6083:
6079:
6076:
6072:Intracellular
6070:
6065:
6061:
6057:
6050:
6045:
6043:
6038:
6036:
6031:
6030:
6027:
6021:
6017:
6016:
6011:
6010:
5999:
5995:
5991:
5987:
5983:
5979:
5974:
5970:
5966:
5962:
5958:
5953:
5948:
5944:
5940:
5936:
5931:
5927:
5923:
5919:
5915:
5911:
5907:
5903:
5899:
5894:
5893:
5868:
5864:
5860:
5856:
5844:
5840:
5836:
5832:
5820:
5816:
5812:
5808:
5807:
5803:
5795:
5791:
5787:
5783:
5779:
5775:
5771:
5767:
5760:
5752:
5748:
5744:
5740:
5735:
5730:
5725:
5720:
5716:
5712:
5708:
5701:
5693:
5689:
5685:
5681:
5676:
5671:
5667:
5663:
5659:
5652:
5644:
5640:
5635:
5630:
5625:
5620:
5616:
5612:
5608:
5601:
5593:
5589:
5584:
5579:
5575:
5571:
5567:
5563:
5559:
5552:
5544:
5540:
5535:
5530:
5526:
5522:
5518:
5514:
5510:
5503:
5501:
5492:
5488:
5484:
5480:
5476:
5472:
5465:
5457:
5453:
5448:
5443:
5438:
5433:
5429:
5425:
5421:
5414:
5406:
5402:
5397:
5392:
5388:
5384:
5380:
5376:
5372:
5368:
5364:
5357:
5355:
5346:
5342:
5337:
5332:
5328:
5324:
5320:
5316:
5312:
5305:
5297:
5293:
5288:
5283:
5279:
5275:
5271:
5267:
5263:
5256:
5248:
5244:
5239:
5234:
5230:
5226:
5222:
5218:
5214:
5210:
5206:
5199:
5183:
5179:
5175:
5168:
5160:
5156:
5152:
5148:
5144:
5140:
5136:
5132:
5125:
5109:
5105:
5101:
5095:
5087:
5083:
5078:
5073:
5069:
5065:
5061:
5057:
5053:
5046:
5039:
5035:
5031:
5026:
5021:
5017:
5013:
5009:
5005:
5001:
4994:
4992:
4990:
4988:
4971:
4967:
4966:New Scientist
4963:
4956:
4948:
4944:
4939:
4934:
4929:
4924:
4920:
4916:
4912:
4905:
4897:
4893:
4888:
4883:
4879:
4875:
4871:
4864:
4848:
4844:
4840:
4834:
4826:
4822:
4818:
4814:
4810:
4806:
4802:
4798:
4794:
4790:
4783:
4775:
4771:
4766:
4761:
4757:
4753:
4749:
4745:
4741:
4734:
4726:
4722:
4718:
4714:
4710:
4706:
4699:
4683:
4679:
4675:
4668:
4660:
4656:
4652:
4648:
4643:
4638:
4634:
4630:
4626:
4620:
4612:
4608:
4604:
4600:
4596:
4592:
4585:
4577:
4573:
4569:
4565:
4561:
4557:
4553:
4549:
4542:
4534:
4530:
4525:
4520:
4516:
4512:
4508:
4504:
4500:
4493:
4485:
4481:
4477:
4473:
4469:
4465:
4457:
4449:
4445:
4441:
4437:
4433:
4429:
4422:
4414:
4410:
4406:
4402:
4398:
4394:
4387:
4379:
4375:
4371:
4367:
4363:
4359:
4352:
4344:
4340:
4336:
4332:
4328:
4324:
4316:
4308:
4304:
4299:
4294:
4289:
4284:
4280:
4276:
4272:
4268:
4264:
4257:
4255:
4253:
4244:
4240:
4236:
4232:
4228:
4224:
4220:
4216:
4208:
4200:
4196:
4192:
4188:
4184:
4180:
4173:
4165:
4161:
4157:
4153:
4149:
4145:
4138:
4136:
4134:
4125:
4121:
4117:
4113:
4109:
4105:
4101:
4097:
4093:
4089:
4082:
4074:
4070:
4065:
4060:
4055:
4050:
4046:
4042:
4038:
4031:
4023:
4019:
4015:
4011:
4007:
4003:
3995:
3987:
3983:
3978:
3973:
3969:
3965:
3961:
3954:
3946:
3942:
3938:
3934:
3930:
3927:(in French).
3926:
3919:
3911:
3907:
3903:
3899:
3894:
3889:
3885:
3881:
3877:
3873:
3866:
3858:
3854:
3850:
3846:
3842:
3838:
3831:
3823:
3819:
3815:
3811:
3807:
3803:
3796:
3788:
3784:
3780:
3776:
3772:
3768:
3761:
3742:
3738:
3734:
3730:
3726:
3719:
3712:
3704:
3700:
3696:
3692:
3687:
3682:
3678:
3674:
3670:
3663:
3647:
3643:
3639:
3635:
3631:
3627:
3623:
3619:
3612:
3604:
3600:
3596:
3592:
3587:
3582:
3578:
3574:
3570:
3563:
3555:
3551:
3547:
3543:
3539:
3535:
3531:
3527:
3520:
3518:
3509:
3505:
3500:
3495:
3491:
3487:
3483:
3479:
3475:
3468:
3460:
3456:
3451:
3446:
3442:
3438:
3434:
3430:
3426:
3419:
3411:
3407:
3402:
3397:
3393:
3389:
3385:
3381:
3377:
3373:
3369:
3362:
3360:
3343:
3339:
3335:
3329:
3321:
3317:
3313:
3309:
3305:
3301:
3297:
3293:
3285:
3277:
3273:
3268:
3263:
3259:
3255:
3251:
3244:
3236:
3232:
3227:
3222:
3218:
3214:
3210:
3203:
3195:
3191:
3186:
3181:
3177:
3173:
3169:
3162:
3146:
3142:
3138:
3132:
3124:
3120:
3116:
3112:
3108:
3104:
3097:
3081:
3077:
3073:
3066:
3064:
3062:
3053:
3049:
3044:
3039:
3034:
3029:
3025:
3021:
3017:
3010:
2994:
2990:
2986:
2980:
2964:
2960:
2954:
2950:
2949:
2941:
2925:
2921:
2915:
2911:
2910:
2902:
2886:
2882:
2878:
2872:
2856:
2852:
2850:
2844:
2838:
2830:
2826:
2822:
2818:
2814:
2810:
2803:
2795:
2791:
2786:
2781:
2776:
2771:
2767:
2763:
2759:
2752:
2736:
2732:
2728:
2721:
2713:
2709:
2704:
2699:
2694:
2689:
2685:
2681:
2677:
2670:
2668:
2666:
2664:
2662:
2660:
2643:
2639:
2635:
2629:
2627:
2618:
2614:
2609:
2604:
2600:
2596:
2592:
2585:
2583:
2574:
2570:
2566:
2562:
2558:
2554:
2547:
2531:
2527:
2523:
2517:
2515:
2513:
2496:
2492:
2488:
2484:
2477:
2461:. 9 June 2023
2460:
2458:
2453:
2452:"Hyftor EPAR"
2447:
2445:
2443:
2426:
2422:
2418:
2412:
2410:
2393:
2389:
2385:
2379:
2363:
2359:
2355:
2349:
2347:
2345:
2343:
2326:
2322:
2318:
2312:
2310:
2308:
2306:
2304:
2302:
2300:
2298:
2296:
2294:
2292:
2290:
2288:
2286:
2270:
2266:
2262:
2256:
2252:
2244:
2242:
2238:
2234:
2230:
2227:
2217:
2215:
2205:
2203:
2199:
2189:
2187:
2178:
2176:
2166:
2164:
2160:
2150:
2148:
2144:
2140:
2136:
2132:
2122:
2113:
2111:
2107:
2103:
2099:
2094:
2092:
2086:
2083:
2079:
2070:
2068:
2064:
2060:
2050:
2048:
2044:
2040:
2036:
2032:
2028:
2024:
2020:
2016:
2012:
2007:
2005:
2001:
1997:
1994:(CCI-779) or
1993:
1989:
1985:
1980:
1969:
1964:
1955:
1953:
1949:
1945:
1940:
1936:
1932:
1928:
1924:
1920:
1916:
1912:
1907:
1903:
1899:
1895:
1891:
1887:
1883:
1879:
1875:
1871:
1867:
1863:
1860:
1856:
1852:
1848:
1844:
1840:
1837:
1833:
1829:
1825:
1821:
1817:
1812:
1809:
1805:
1796:
1783:
1775:
1771:
1764:
1750:
1744:
1737:
1735:
1731:
1726:
1722:
1718:
1714:
1710:
1700:
1698:
1695:
1691:
1680:
1671:
1667:
1664:This section
1662:
1659:
1655:
1654:
1646:
1644:
1638:
1636:
1632:
1628:
1624:
1620:
1616:
1613:
1603:
1601:
1600:
1593:
1591:
1587:
1583:
1578:
1576:
1572:
1568:
1564:
1560:
1556:
1550:
1535:
1533:
1529:
1525:
1521:
1518:
1508:
1506:
1496:
1494:
1490:
1486:
1482:
1478:
1468:
1460:
1458:
1454:
1450:
1443:Lung toxicity
1440:
1438:
1434:
1430:
1426:
1422:
1407:
1403:
1399:
1398:ovarian cysts
1395:
1392:
1390:
1387:
1386:
1383:
1379:
1375:
1372:
1369:
1368:
1365:
1361:
1358:
1356:
1353:
1352:
1349:
1345:
1343:
1340:
1339:
1336:
1332:
1328:
1324:
1321:
1320:
1317:
1313:
1309:
1306:
1304:
1300:
1297:
1296:
1293:
1290:
1288:
1285:
1284:
1281:
1277:
1273:
1269:
1266:
1264:
1261:
1260:
1256:
1252:
1251:herpes zoster
1248:
1244:
1241:
1238:
1237:
1233:
1230:
1229:
1226:
1223:
1221:
1217:
1213:
1209:
1203:
1201:
1197:
1193:
1189:
1185:
1181:
1177:
1173:
1169:
1158:
1155:
1152:
1148:
1147:angiofibromas
1141:Angiofibromas
1138:
1129:
1127:
1123:
1119:
1114:
1108:
1098:
1095:
1093:
1088:
1086:
1082:
1078:
1074:
1070:
1065:
1061:
1056:
1054:
1050:
1046:
1042:
1038:
1037:smooth muscle
1034:
1024:
1021:
1017:
1013:
1009:
1004:
1002:
998:
994:
988:
984:
974:
972:
968:
962:
960:
957:
952:
950:
946:
942:
938:
935:Sirolimus is
928:
926:
922:
918:
914:
910:
906:
905:Easter Island
902:
898:
897:
893:
888:
886:
882:
877:
875:
874:interleukin-2
871:
867:
863:
859:
855:
851:
847:
843:
839:
835:
831:
827:
823:
813:
806:
797:
792:
791:
788:
781:
772:
771:
768:
761:
757:
755:
751:
744:
740:
739:
737:
734:
729:
722:
720:
716:
692:
690:
686:
681:
677:
673:
670:
668:
666:ECHA InfoCard
662:
654:
650:
649:DTXSID5023582
646:
645:
643:
634:
630:
622:
621:RCSB PDB
616:
611:
610:
608:
606:
602:
595:
591:
590:
588:
586:
582:
575:
571:
570:
568:
566:
562:
555:
551:
550:
548:
546:
542:
535:
531:
530:
528:
526:
522:
515:
511:
510:
508:
506:
502:
495:
491:
490:
488:
486:
482:
475:
471:
470:
468:
461:
457:
450:
446:
445:
443:
441:
437:
423:
419:
415:
411:
405:
401:
397:
393:
389:
385:
381:
377:
373:
369:
365:
361:
356:
355:
352:
345:
340:
336:
334:
330:
326:
324:
317:
314:
311:
309:
305:
301:
299:
295:
291:
289:
285:
281:
277:
271: Rx-only
264:
261:
249:
248:
246:
244:
240:
235:
227:
222:
217:
212:
207:
202:
197:
192:
189:
188:
186:
184:
180:
177:
173:
169:
166:
164:
158:
152:
143:
142:
140:
138:
132:
125:
121:
111:
108:
103:
94:
91:
86:
77:
76:
74:
72:
68:
64:
60:
56:
54:
50:
47:Clinical data
45:
41:
36:
32:
27:
19:
9971:Orphan drugs
9905:
9885:Ketoconazole
9882:Antagonists:
9881:
9855:Troglitazone
9830:Tetracycline
9785:Spiroxatrine
9774:
9730:Quingestrone
9725:Progesterone
9710:Pregnenolone
9705:Pregnanolone
9695:Pregnanediol
9690:Prednisolone
9615:Mifepristone
9542:
9517:Griseofulvin
9497:Fenbendazole
9482:Famprofazone
9477:Erythromycin
9472:Epothilone B
9457:Eburnamonine
9352:Clotrimazole
9342:Clofenvinfos
9277:Antimycotics
9208:
9171:Okadaic acid
9123:Antagonists:
9122:
9111:Troglitazone
9046:Mifepristone
9041:Methoxychlor
9036:Griseofulvin
9031:Ellagic acid
9011:Cypermethrin
9001:Clotrimazole
8952:
8842:Pexidartinib
8827:Odronextamab
8797:Gilteritinib
8777:Cabozantinib
8724:
8690:
8665:
8659:Temsirolimus
8641:
8625:
8607:proapoptotic
8605:
8589:
8568:Zanubrutinib
8540:
8510:
8479:
8456:Lestaurtinib
8435:Janus kinase
8433:
8414:
8368:
8361:Non-receptor
8342:Cabozantinib
8335:
8304:Infigratinib
8289:
8263:
8205:Fruquintinib
8187:
8180:Gilteritinib
8176:Lestaurtinib
8169:
8118:
8087:
8060:Mobocertinib
8025:Aumolertinib
8013:
7978:Tremelimumab
7963:Tislelizumab
7918:Retifanlimab
7793:Blinatumomab
7763:Atezolizumab
7734:
7716:
7706:
7688:Obinutuzumab
7666:
7648:
7615:
7598:
7556:
7539:
7456:Upadacitinib
7416:Satralizumab
7401:Ritlecitinib
7396:Risankizumab
7191:
7172:
7112:Teprotumumab
7062:Inebilizumab
7057:Fontolizumab
7037:Atorolimumab
7005:T-lymphocyte
7003:
6977:
6961:
6947:
6928:
6917:Lerdelimumab
6912:Bertilimumab
6904:
6892:
6871:
6857:
6843:
6829:
6810:
6791:
6775:Pascolizumab
6760:Obinutuzumab
6752:
6738:
6724:
6708:Clenoliximab
6700:
6684:Otelixizumab
6671:
6644:
6631:Lebrikizumab
6615:
6599:
6583:
6567:
6551:
6508:Satralizumab
6498:Risankizumab
6430:
6389:
6373:
6365:Serum target
6317:Temsirolimus
6311:
6243:
6234:Pomalidomide
6229:Lenalidomide
6187:Pimecrolimus
6166:
6140:Methotrexate
6132:
6110:
6097:Azathioprine
6089:
6074:(initiation)
6013:
5981:
5977:
5942:
5938:
5901:
5897:
5871:. Retrieved
5862:
5847:. Retrieved
5838:
5823:. Retrieved
5814:
5802:
5769:
5765:
5759:
5714:
5710:
5700:
5665:
5661:
5651:
5614:
5610:
5600:
5565:
5561:
5551:
5516:
5512:
5474:
5470:
5464:
5427:
5423:
5413:
5370:
5366:
5318:
5314:
5304:
5269:
5265:
5255:
5212:
5208:
5198:
5186:. Retrieved
5177:
5167:
5134:
5130:
5124:
5112:. Retrieved
5103:
5094:
5059:
5055:
5045:
5037:
5007:
5003:
4974:. Retrieved
4965:
4955:
4918:
4914:
4904:
4877:
4873:
4863:
4851:. Retrieved
4842:
4833:
4792:
4788:
4782:
4747:
4743:
4733:
4708:
4704:
4698:
4686:. Retrieved
4677:
4667:
4632:
4628:
4619:
4597:(1): 47–60.
4594:
4590:
4584:
4551:
4547:
4541:
4506:
4502:
4492:
4467:
4463:
4456:
4431:
4427:
4421:
4396:
4392:
4386:
4361:
4357:
4351:
4326:
4322:
4315:
4270:
4266:
4218:
4214:
4207:
4185:(1): 51–61.
4182:
4178:
4172:
4147:
4143:
4091:
4087:
4081:
4044:
4040:
4030:
4005:
4001:
3994:
3967:
3963:
3953:
3931:(1): 64–69.
3928:
3924:
3918:
3875:
3871:
3865:
3840:
3836:
3830:
3805:
3801:
3795:
3770:
3766:
3760:
3748:. Retrieved
3728:
3724:
3711:
3676:
3672:
3662:
3652:24 September
3650:. Retrieved
3625:
3621:
3611:
3576:
3572:
3562:
3529:
3525:
3484:(1): 28–38.
3481:
3477:
3467:
3432:
3428:
3418:
3375:
3371:
3346:. Retrieved
3337:
3328:
3298:(1): 14–20.
3295:
3291:
3284:
3260:(1): 86–90.
3257:
3253:
3243:
3216:
3212:
3202:
3175:
3171:
3161:
3149:. Retrieved
3145:the original
3140:
3131:
3106:
3102:
3096:
3084:. Retrieved
3023:
3019:
3009:
2997:. Retrieved
2979:
2967:. Retrieved
2947:
2940:
2928:. Retrieved
2908:
2901:
2889:. Retrieved
2880:
2871:
2859:. Retrieved
2846:
2837:
2812:
2808:
2802:
2765:
2761:
2751:
2739:. Retrieved
2730:
2720:
2683:
2679:
2646:. Retrieved
2642:the original
2638:Cypher Stent
2598:
2594:
2556:
2552:
2546:
2534:. Retrieved
2525:
2499:. Retrieved
2490:
2486:
2476:
2463:. Retrieved
2455:
2429:. Retrieved
2420:
2396:. Retrieved
2387:
2378:
2366:. Retrieved
2357:
2329:. Retrieved
2320:
2272:. Retrieved
2264:
2255:
2224:A number of
2223:
2211:
2195:
2184:
2172:
2156:
2128:
2119:
2100:goes up and
2095:
2087:
2082:mouse models
2076:
2056:
2031:chemotherapy
2008:
1992:temsirolimus
1981:
1977:
1948:methylations
1931:condensation
1905:
1901:
1897:
1893:
1889:
1885:
1881:
1877:
1865:
1861:
1838:
1831:
1827:
1823:
1813:
1801:
1730:biosynthesis
1721:biosynthesis
1709:biosynthesis
1706:
1703:Biosynthesis
1687:
1674:
1670:adding to it
1665:
1639:
1609:
1597:
1594:
1579:
1552:
1538:Pharmacology
1532:blood plasma
1514:
1511:Interactions
1502:
1485:azathioprine
1477:skin cancers
1474:
1466:
1446:
1437:temsirolimus
1418:
1224:
1204:
1182:, increased
1180:hypertension
1164:
1156:
1144:
1135:
1110:
1096:
1089:
1057:
1030:
1005:
990:
967:angiofibroma
963:
953:
934:
931:Medical uses
925:angiofibroma
900:
894:
889:
878:
848:, and treat
829:
825:
821:
820:
809:
421:
417:
413:
409:
403:
399:
395:
391:
387:
383:
379:
375:
371:
367:
363:
359:
337:Mostly fecal
320:Elimination
243:Legal status
237:Legal status
71:License data
18:
9870:Zafirlukast
9840:Thiothixene
9820:Terconazole
9770:Simvastatin
9645:Nisoldipine
9640:Nilvadipine
9625:Nicardipine
9595:Metacycline
9422:Dimercaprol
9377:Demecolcine
9337:Clindamycin
9332:Ciglitazone
9282:Artemisinin
9262:Ambrisentan
9166:Nigramide J
9101:Telmisartan
9061:Nicardipine
8971:Benfuracarb
8966:Artemisinin
8872:Tebentafusp
8852:Regorafenib
8847:Quizartinib
8837:Pemigatinib
8817:Midostaurin
8792:Erdafitinib
8787:Entrectinib
8770:Parsaclisib
8718:Trilaciclib
8708:Palbociclib
8703:Dalpiciclib
8698:Abemaciclib
8600:Aflibercept
8527:Entrectinib
8497:Selumetinib
8492:Cobimetinib
8487:Binimetinib
8471:Ruxolitinib
8461:Momelotinib
8441:Baricitinib
8339:inhibitors:
8316:Pralsetinib
8312:Pemigatinib
8300:Futibatinib
8296:Entrectinib
8293:inhibitors:
8225:Regorafenib
8129:Avapritinib
8075:Rociletinib
8070:Osimertinib
8035:Dacomitinib
7973:Toripalimab
7958:Teclistamab
7948:Talquetamab
7943:Tafasitamab
7938:Sugemalimab
7933:Serplulimab
7923:Sabatolimab
7913:Ramucirumab
7908:Prolgolimab
7878:Necitumumab
7833:Epcoritamab
7813:Dostarlimab
7803:Daratumumab
7758:Amivantamab
7723:Alemtuzumab
7713:Brentuximab
7703:Tositumomab
7678:Ibritumomab
7659:Elranatamab
7622:Bevacizumab
7610:Edrecolomab
7605:Catumaxomab
7567:Trastuzumab
7551:Panitumumab
7451:Tofacitinib
7391:Ravulizumab
7381:Pirfenidone
7371:Peficitinib
7271:Canakinumab
7261:Briakinumab
7251:Bimekizumab
7246:Baricitinib
7211:Aflibercept
7122:Vepalimomab
7117:Vapaliximab
7092:Rovelizumab
7082:Pexelizumab
7072:Morolimumab
7047:Cedelizumab
7032:Anifrolumab
7027:Alemtuzumab
6985:Basiliximab
6955:Tocilizumab
6941:Vedolizumab
6936:Natalizumab
6922:Metelimumab
6865:Gavilimomab
6823:Toralizumab
6818:Teneliximab
6804:Lumiliximab
6799:Gomiliximab
6785:Ublituximab
6765:Ocrelizumab
6718:Zanolimumab
6694:Visilizumab
6652:Secukinumab
6636:Ustekinumab
6607:Elsilimomab
6591:Faralimomab
6559:Mepolizumab
6543:Ustekinumab
6538:Tocilizumab
6513:Secukinumab
6463:Canakinumab
6453:Briakinumab
6448:Bimekizumab
6443:Basiliximab
6432:Interleukin
6422:Nerelimomab
6327:Zotarolimus
6268:(reception)
6239:Thalidomide
6197:Voclosporin
6182:Ciclosporin
6176:Calcineurin
6172:Cyclophilin
6119:Leflunomide
6115:inhibitors
6015:NCT02494570
5873:23 February
5849:23 February
5825:23 February
5734:2268/256132
5315:GeroScience
4688:19 February
4470:(1): 9–16.
4064:2445/178597
2891:26 November
2522:"Rapamycin"
2431:26 November
2368:19 December
2331:26 November
2035:doxorubicin
2029:effects of
2015:doxorubicin
1915:cyclohexane
1845:-dependent
1694:macrocyclic
1677:August 2016
1631:ciclosporin
1623:efflux pump
1575:calcineurin
1528:efflux pump
1471:Cancer risk
1406:menorrhagia
1355:Respiratory
1331:hypokalemia
1314:(TTP/HUS),
1299:Hematologic
1253:infection,
1092:orphan drug
1077:cholesterol
726: g·mol
672:100.107.147
342:Identifiers
327:57–63 hours
172:intravenous
62:Other names
53:Trade names
9966:Macrolides
9945:Categories
9850:Tianeptine
9815:Tenylidone
9810:Tacrolimus
9755:Rimexolone
9745:Rifampicin
9685:Plicamycin
9670:Paclitaxel
9655:Omeprazole
9635:Nifedipine
9610:Mevastatin
9605:Metyrapone
9585:Lovastatin
9580:Loratadine
9537:Hyperforin
9527:Haloprogin
9492:Felodipine
9467:Enzacamene
9447:Dronabinol
9412:Diclazuril
9391:prasterone
9347:Chloroxine
9322:Cephradine
9292:Bile acids
9106:Tolnaftate
9071:Permethrin
9056:Nevirapine
9051:Nefazodone
9020:prasterone
8981:Carvedilol
8961:Amiodarone
8932:modulators
8887:Venetoclax
8882:Vandetanib
8857:Ripretinib
8822:Nintedanib
8807:Lenvatinib
8782:Capmatinib
8765:Idelalisib
8755:Copanlisib
8728:inhibitors
8713:Ribociclib
8684:Vismodegib
8669:inhibitors
8649:Everolimus
8615:prohibitin
8532:Lorlatinib
8522:Crizotinib
8502:Trametinib
8466:Pacritinib
8451:Filgotinib
8446:Fedratinib
8350:Crizotinib
8346:Capmatinib
8328:Vandetanib
8276:Brigatinib
8255:Vandetanib
8215:Nintedanib
8210:Lenvatinib
8149:Ripretinib
8080:Vandetanib
8055:Lazertinib
8030:Brigatinib
7953:Tarlatamab
7888:Olaratumab
7848:Isatuximab
7843:Ipilimumab
7823:Elotuzumab
7818:Durvalumab
7798:Cemiplimab
7788:Bermekimab
7778:Axatilimab
7693:Ofatumumab
7673:Glofitamab
7655:Glofitamab
7563:Pertuzumab
7441:Sutimlimab
7436:Spesolimab
7421:Siltuximab
7361:Olokizumab
7351:Ixekizumab
7346:Itacitinib
7336:Guselkumab
7331:Fingolimod
7326:Filgotinib
7276:Crovalimab
7266:Brodalumab
7256:Blisibimod
7221:Rilonacept
7204:Opinercept
7199:Etanercept
7185:Belatacept
7136:Polyclonal
7097:Siplizumab
7087:Reslizumab
7077:Ofatumumab
7067:Maslimomab
7052:Emapalumab
6995:Inolimomab
6990:Daclizumab
6969:Odulimomab
6884:Ruplizumab
6879:Frexalimab
6837:Aselizumab
6732:Efalizumab
6689:Teplizumab
6585:Interferon
6575:Omalizumab
6528:Spesolimab
6518:Siltuximab
6493:Rilonacept
6488:Olokizumab
6478:Ixekizumab
6473:Guselkumab
6468:Daclizumab
6458:Brodalumab
6417:Infliximab
6402:Afelimomab
6397:Adalimumab
6381:Eculizumab
6357:Monoclonal
6348:Antibodies
6322:Umirolimus
6302:Everolimus
6251:Apremilast
6211:Gusperimus
6192:Tacrolimus
6160:inhibitors
6152:Macrolides
6134:antifolate
5519:(12): 73.
5373:: 109282.
5056:Aging Cell
4960:Lawton G.
4880:(5): 332.
3893:2183/19864
3478:Aging Cell
3219:(1): 328.
2861:1 February
2686:: 701464.
2274:22 October
2247:References
2125:SARS-CoV-2
2091:everolimus
2067:everolimus
1996:everolimus
1990:, such as
1952:oxidations
1804:macrocycle
1734:polyketide
1725:polyketide
1555:tacrolimus
1547:See also:
1433:everolimus
1402:amenorrhea
1389:Urogenital
1316:leukopenia
1292:Stomatitis
1257:infection
1247:lymphocele
1208:stomatitis
1196:arthralgia
1184:creatinine
1087:patients.
1014:), and/or
1012:tacrolimus
981:See also:
961:(PEComa).
941:prevention
909:antifungal
885:restenosis
840:, prevent
731:3D model (
719:Molar mass
605:PDB ligand
574:CHEBI:9168
534:W36ZG6FT64
505:ChemSpider
449:53123-88-9
440:CAS Number
351:IUPAC name
308:Metabolism
9775:Sirolimus
9765:Ritonavir
9760:Riodipine
9750:Rifaximin
9735:Reserpine
9720:Proadifen
9665:Oxatomide
9620:Nafcillin
9590:Meclizine
9452:Droxidopa
9432:Docetaxel
9357:Colforsin
9307:Bumecaine
9297:Bithionol
9209:Agonists:
9186:T-0901317
9161:Meclizine
9091:Reserpine
9081:Phenytoin
9066:Octicizer
9026:Efavirenz
8953:Agonists:
8877:Tepotinib
8867:Sunitinib
8862:Sorafenib
8832:Pazopanib
8812:Masitinib
8760:Duvelisib
8750:Alpelisib
8738:Sotorasib
8733:Adagrasib
8679:Sonidegib
8674:Glasdegib
8620:Adipotide
8553:Ibrutinib
8426:Dasatinib
8421:Bosutinib
8406:Radotinib
8401:Ponatinib
8396:Nilotinib
8386:Dasatinib
8381:Bosutinib
8376:Asciminib
8344:(VEGFR),
8302:(FGFR2),
8281:Ceritinib
8271:Alectinib
8250:Toceranib
8245:Tivozanib
8240:Sunitinib
8235:Sorafenib
8230:Semaxanib
8220:Pazopanib
8200:Cediranib
8164:Toceranib
8159:Sunitinib
8154:Sorafenib
8144:Pazopanib
8139:Masitinib
8106:Tucatinib
8101:Neratinib
8096:Lapatinib
8065:Olmutinib
8045:Gefitinib
8040:Erlotinib
8015:HER1/EGFR
7883:Nivolumab
7873:Naxitamab
7698:Rituximab
7546:Cetuximab
7541:HER1/EGFR
7431:Sirukumab
7426:Siponimod
7411:Sarilumab
7386:Ponesimod
7356:Netakimab
7341:Iptacopan
7321:Etrasimod
7281:Danicopan
7216:Alefacept
7180:Abatacept
7102:Talizumab
7042:Begelomab
6898:Belimumab
6851:Galiximab
6780:Rituximab
6746:Erlizumab
6713:Keliximab
6523:Sirukumab
6503:Sarilumab
6483:Netakimab
6412:Golimumab
6312:Sirolimus
5969:207831199
5751:231766741
5159:206685475
4921:(1): 39.
4659:198175394
4651:1743-4289
2768:(1): 29.
2237:longevity
2027:cytotoxic
2023:remission
1939:dehydrate
1802:The core
1649:Chemistry
1627:half life
1582:cytosolic
1364:epistaxis
1360:Pneumonia
1322:Metabolic
1303:lymphatic
1287:Digestive
1186:, fever,
1010:(such as
973:complex.
956:malignant
937:indicated
903:found on
892:bacterium
834:macrolide
826:rapamycin
822:Sirolimus
594:ChEMBL413
333:Excretion
322:half-life
161:Routes of
135:Pregnancy
124:Sirolimus
107:Sirolimus
23:Sirolimus
9981:Polyenes
9935:Medicine
9902:See also
9790:SR-12813
9680:Piperine
9660:Orlistat
9630:Nicotine
9502:Fentanyl
9487:Febantel
9462:Ecopipam
9427:Dinaline
9312:Cafestol
9302:Bosentan
9176:PK-11195
8667:hedgehog
8629:against
8627:exotoxin
8593:against
8542:Bruton's
8391:Imatinib
8314:(FGFR),
8310:(NTRK),
8195:Axitinib
8134:Axitinib
8090:HER2/neu
8050:Icotinib
8020:Afatinib
7994:("-nib")
7773:Avelumab
7645:lymphoid
7637:lymphoma
7633:Leukemia
7558:HER2/neu
7520:("-mab")
7366:Ozanimod
7241:Avacopan
7234:Unsorted
7020:Unsorted
6930:Integrin
6663:Cellular
6438:Anakinra
6284:Anakinra
6206:Abetimus
6058: /
5998:33737259
5961:31676179
5918:22037041
5867:Archived
5843:Archived
5819:Archived
5794:30469863
5743:33512760
5692:31313976
5643:27245261
5592:35526176
5543:27812954
5491:15383655
5456:30666207
5430:: 1520.
5405:33031791
5345:31761958
5296:26403194
5247:23325216
5182:Archived
5151:25540326
5114:23 March
5108:Archived
5086:33145977
5034:27208895
4970:Archived
4947:30760308
4896:45906785
4853:23 March
4847:Archived
4817:15029198
4774:15365568
4725:16103051
4682:Archived
4611:16039868
4576:19250234
4568:17041628
4548:Oncogene
4533:22379028
4448:16536560
4413:19387497
4378:16990929
4343:15127450
4243:34950948
4235:12021624
4199:16418694
4073:22830463
4022:20970608
3986:21444868
3945:22240222
3910:39914334
3902:19661024
3857:12581772
3822:16962483
3787:17346635
3741:Archived
3737:16318648
3703:24496443
3695:15114088
3646:Archived
3642:21911165
3603:12116798
3595:11571438
3554:24408680
3546:16127266
3508:26463117
3459:18385422
3410:22461615
3342:Archived
3312:25174683
3276:27723921
3235:31864650
3194:32200879
3151:22 April
3123:17093244
3086:1 August
3080:Archived
3052:31461151
2999:1 August
2993:Archived
2969:1 August
2963:Archived
2930:1 August
2924:Archived
2885:Archived
2855:Archived
2829:15896681
2794:23369283
2735:Archived
2731:Radiolab
2712:20130772
2573:11165091
2536:1 August
2530:Archived
2495:Archived
2425:Archived
2398:23 March
2392:Archived
2388:DailyMed
2362:Archived
2358:DailyMed
2325:Archived
2321:DailyMed
1968:Rano Kau
1958:Research
1946:through
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