287:
24:
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128:
885:
Lee, D.; Lee, K.; Cai, X. F.; Dat, N. T.; Boovanahalli, S. K.; Lee, M.; Shin, J. C.; Kim, W.; Jeong, J. K.; Lee, J. S.; Lee, C. H.; Lee, J. H.; Hong, Y. S.; Lee, J. J. (2006). "Biosynthesis of the Heat-Shock
Protein 90 Inhibitor Geldanamycin: New Insight into the Formation of the Benzoquinone
320:
InChI=1S/C29H40N2O9/c1-15-11-19-25(34)20(14-21(32)27(19)39-7)31-28(35)16(2)9-8-10-22(37-5)26(40-29(30)36)18(4)13-17(3)24(33)23(12-15)38-6/h8-10,13-15,17,22-24,26,33H,11-12H2,1-7H3,(H2,30,36)(H,31,35)/b10-8-,16-9+,18-13+/t15-,17+,22+,23+,24-,26+/m1/s1
310:
InChI=1S/C29H40N2O9/c1-15-11-19-25(34)20(14-21(32)27(19)39-7)31-28(35)16(2)9-8-10-22(37-5)26(40-29(30)36)18(4)13-17(3)24(33)23(12-15)38-6/h8-10,13-15,17,22-24,26,33H,11-12H2,1-7H3,(H2,30,36)(H,31,35)/b10-8-,16-9+,18-13+/t15-,17+,22+,23+,24-,26+/m1/s1
573:, and methoxymalonyl-CoA to synthesize the precursor molecule Progeldanamycin. This precursor is subjected to several enzymatic and non-enzymatic tailoring steps to produce the active molecule geldanamycin, which include hydroxylation,
841:
Kim, W.; Lee, D.; Hong, S. S.; Na, Z.; Shin, J. C.; Roh, S. H.; Wu, C. Z.; Choi, O.; Lee, K.; Shen, Y. M.; Paik, S. G.; Lee, J. J.; Hong, Y. S. (2009). "Rational
Biosynthetic Engineering for Optimization of Geldanamycin Analogues".
471:(Heat Shock Protein 90) by binding to the unusual ADP/ATP-binding pocket of the protein. HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival,
535:
under physiological concentrations. These side effects have led to the development of geldanamycin analogues, in particular analogues containing a derivatisation at the 17 position:
798:
He, W.; Wu, L.; Gao, Q.; Du, Y.; Wang, Y. (2006). "Identification of AHBA Biosynthetic Genes
Related to Geldanamycin Biosynthesis in Streptomyces hygroscopicus 17997".
565:. The genes gelA, gelB, and gelC encode for the polyketide synthase. The PKS is first loaded with 3-amino-5-hydroxybenzoic acid (AHBA). It then utilizes
519:. This effect is mediated via HSP90. Despite its potent antitumor potential, geldanamycin presents several major drawbacks as a drug candidate such as
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998:
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343:
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596:"Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin"
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710:"Crystal structure of an Hsp90-geldanamycin complex: Targeting of a protein chaperone by an antitumor agent"
935:"Geldanamycin, an inhibitor of the chaperone activity of HSP90, induces MAPK-independent cell cycle arrest"
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168:
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Schulte, T. W.; Akinaga, S.; Soga, S.; Sullivan, W.; Stensgard, B.; Toft, D.; Neckers, L. M. (1998).
282:
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Stebbins, C. E.; Russo, A. A.; Schneider, C.; Rosen, N.; Hartl, F. U.; Pavletich, N. P. (1997).
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Geldanamycin induces the degradation of proteins that are mutated or overexpressed in
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759:"Geldanamycin-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane"
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Wayne, N.; Mishra, P.; Bolon, D.N. (2011). "Hsp90 and Client
Protein Maturation".
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NC(=O)O1C(/C)=C/(C)(O)(OC)C(C)C\C2=C(/OC)C(=O)\C=C(\NC(=O)C(\C)=C\C=C/1OC)C2=O
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Except where otherwise noted, data are given for materials in their
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561:. It is a macrocyclic polyketide that is synthesized by a Type I
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Bedin, M.; Gaben, A. M.; Saucier, C. C.; Mester, J. (2004).
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10.1379/1466-1268(1998)003<0100:ARBTTN>2.3.CO;2
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Geldanamycin was originally discovered in the organism
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Jilani, Kashif; Qadri, Syed M.; Lang, Florian (2013).
661:. Methods Mol Biol. Vol. 787. pp. 33–44.
999:Center for Pharmaceutical Research and Innovation
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642:: CS1 maint: DOI inactive as of April 2024 (
577:-methylation, carbamoylation, and oxidation.
82:docosa-1(21),4,6,10,18-pentaen-9-yl carbamate
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527:. reported that geldanamycin induces the
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78:8,14,19-trimethoxy-4,10,12,16-tetramethyl
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330:Key: QTQAWLPCGQOSGP-KSRBKZBZSA-N
313:Key: QTQAWLPCGQOSGP-KSRBKZBZSA-N
167:
147:
406:Gold-yellow fine crystalline powder
323:Key: QTQAWLPCGQOSGP-KSRBKZBZBP
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13:
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490:Hsp90-geldanamycin complex. PDB
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939:International Journal of Cancer
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416:(at 25 °C , 100 kPa).
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600:Cell Stress & Chaperones
80:-3,20,22-trioxo-2-azabicyclo
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667:10.1007/978-1-61779-295-3_3
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558:Streptomyces hygroscopicus
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614:(inactive 2024-04-26).
900:10.1002/cbic.200500441
856:10.1002/cbic.200800763
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800:Current Microbiology
763:Cell Physiol Biochem
659:Molecular Chaperones
465:antitumor antibiotic
563:polyketide synthase
18:
1048:Secondary alcohols
996:Geldanamycin from
988:Geldanamycin from
523:, further, Jilani
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443:Infobox references
16:
1023:1,4-Benzoquinones
952:10.1002/ijc.20010
776:10.1159/000356596
676:978-1-61779-294-6
571:methylmalonyl-CoA
451:Chemical compound
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169:ChEMBL278315
88:Identifiers
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888:ChemBioChem
844:ChemBioChem
567:malonyl-CoA
481:oncogenesis
403:Appearance
360:Properties
1053:Ansamycins
1028:Carbamates
1017:Categories
927:References
394:Molar mass
254:Z3K3VJ16KU
180:ChemSpider
149:CHEBI:5292
116:3D model (
105:30562-34-6
95:CAS Number
37:IUPAC name
991:Fermentek
886:Moiety".
529:apoptosis
473:apoptosis
462:ansamycin
969:39451213
961:14999769
916:42998903
908:16381049
864:19308924
828:22291736
820:16502293
785:24335345
695:21898225
200:DrugBank
189:10272739
1033:Lactams
1006:in the
872:3273370
744:5253110
736:9108479
686:5078872
630:9672245
545:17-DMAG
509:Bcr-Abl
436:what is
434: (
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234:5288382
221:PubChem
209:DB02424
1043:Ethers
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525:et al.
515:, and
431:verify
428:
344:SMILES
160:ChEMBL
31:Names
965:S2CID
912:S2CID
868:S2CID
824:S2CID
740:S2CID
581:Notes
517:ERBB2
505:v-Src
501:tumor
469:Hsp90
457:is a
302:InChI
140:ChEBI
118:JSmol
957:PMID
904:PMID
860:PMID
816:PMID
781:PMID
732:PMID
714:Cell
691:PMID
671:ISBN
644:link
626:PMID
493:1yet
479:and
245:UNII
1008:PDB
947:doi
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896:doi
852:doi
808:doi
771:doi
722:doi
681:PMC
663:doi
616:PMC
608:doi
531:of
513:p53
271:EPA
224:CID
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