710:
Novelty of target and MoA is the second major potential advantage of PDD . In addition to identifying novel targets, PDD can contribute to improvements over existing therapies by identifying novel physiology for a known target, exploring 'undrugged' targets that belong to well known drug target
314:
on fish survival. Pharmaceuticals are usually found at ng/L to low-ΞΌg/L concentrations in the aquatic environment. Adverse effects may occur in non-target species as a consequence of specific drug target interactions. Therefore,
129:
change in the target is induced by the stimulus which results in a change in target function. This change in function can mimic the effect of the endogenous substance in which case the effect is referred to as
95:β A chemical reaction occurs between the stimulus and target in which the stimulus becomes chemically bonded to the target, but the reverse reaction also readily occurs in which the bond can be broken.
88:β A relatively weak interaction between the stimulus and the target where no chemical bond is formed between the two interacting partners and hence the interaction is completely reversible.
861:
Gunnarsson L, Jauhiainen A, Kristiansson E, Nerman O, Larsson DG (August 2008). "Evolutionary conservation of human drug targets in organisms used for environmental risk assessments".
333:
294:
These biological targets are conserved across species, making pharmaceutical pollution of the environment a danger to species who possess the same targets. For example, the synthetic
251:
approach. Potential drug targets are not necessarily disease causing but must by definition be disease modifying. An alternative means of identifying new drug targets is
904:
Larsson DG, Adolfsson-Erici M, Parkkonen J, Pettersson M, Berg AM, Olsson PE, FΓΆrlin L (April 1999). "Ethinyloestradiol β an undesired fish contraceptive?".
456:
247:
Identifying the biological origin of a disease, and the potential targets for intervention, is the first step in the discovery of a medicine using the
155:
research to describe the native protein in the body whose activity is modified by a drug resulting in a specific effect, which may be a desirable
110:
substances (such as activating hormones) from binding to the target. Depending on the nature of the target, this effect is referred as
81:, the drug or ligand) physically binds to ("hits") the biological target. The interaction between the substance and the target may be:
31:) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets are
255:
based on phenotypic screening to identify "orphan" ligands whose targets are subsequently identified through target deconvolution.
815:
Jung HJ, Kwon HJ (2015). "Target deconvolution of bioactive small molecules: the heart of chemical biology and drug discovery".
587:
468:
439:
570:
Lundstrom K (2009). "An overview on GPCRs and drug discovery: structure-based drug design and structural biology on GPCRs".
723:
Lee H, Lee JW (2016). "Target identification for biologically active small molecules using chemical biology approaches".
98:
irreversible covalent β The stimulus is permanently bound to the target through irreversible chemical bond formation.
387:
Moy VT, Florin EL, Gaub HE (October 1994). "Intermolecular forces and energies between ligands and receptors".
310:
of fish downstream from sewage treatment plants, thereby unbalancing reproduction and creating an additional
1033:
430:
Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G (2012). "Chapter 3: How drugs act: molecular aspects".
267:
319:
drug targets are likely to be associated with an increased risk for non-targeted pharmacological effects.
57:), or some other target of an external stimulus. Biological targets are most commonly proteins such as
231:
174:
316:
210:
711:
classes or discovering novel MoAs, including new ways of interfering with difficult-to-drug targets.
106:
There is no direct change in the biological target, but the binding of the substance prevents other
205:
40:
138:) or be the opposite of the endogenous substance which in the case of receptors is referred to as
980:
Kostich MS, Lazorchak JM (2008). "Risks to aquatic organisms posed by human pharmaceutical use".
66:
303:
307:
484:
Overington JP, Al-Lazikani B, Hopkins AL (December 2006). "How many drug targets are there?".
1028:
527:
Landry Y, Gies JP (February 2008). "Drugs and their molecular targets: an updated overview".
311:
24:
989:
944:
870:
396:
252:
248:
8:
111:
85:
993:
948:
874:
400:
840:
792:
767:
748:
701:
647:
622:
598:
552:
509:
352:
Raffa RB, Porreca F (1989). "Thermodynamic analysis of the drug-receptor interaction".
156:
917:
1005:
962:
886:
832:
797:
740:
693:
652:
603:
583:
556:
544:
540:
501:
464:
435:
412:
369:
365:
222:
126:
46:
1001:
752:
672:"Opportunities and challenges in phenotypic drug discovery: an industry perspective"
513:
39:. The definition is context-dependent, and can refer to the biological target of a
23:
is anything within a living organism to which some other entity (like an endogenous
997:
952:
913:
878:
844:
824:
787:
779:
732:
705:
683:
642:
634:
593:
575:
536:
493:
404:
361:
217:
135:
119:
115:
139:
579:
638:
328:
184:
160:
152:
107:
828:
736:
1022:
299:
92:
408:
1009:
966:
890:
836:
801:
744:
697:
656:
607:
548:
505:
36:
416:
373:
903:
688:
671:
196:
62:
434:. Edinburgh; New York: Elsevier/Churchill Livingstone. pp. 20β48.
957:
932:
882:
860:
783:
463:. Edinburgh; New York: Elsevier/Churchill Livingstone. pp. 6β19.
283:
497:
167:. The most common drug targets of currently marketed drugs include:
163:. In this context, the biological target is often referred to as a
295:
278:
192:
188:
16:
Part of an organism targeted by a ligand or drug to affect behavior
334:
Environmental impact of pharmaceuticals and personal care products
102:
Depending on the nature of the stimulus, the following can occur:
226:
131:
54:
50:
32:
574:. Methods in Molecular Biology. Vol. 552. pp. 51β66.
273:
180:
58:
768:"Identification of direct protein targets of small molecules"
483:
455:
Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G (2012).
43:
28:
930:
670:
Moffat JG, Vincent F, Lee JA, Eder J, Prunotto M (2017).
933:"Repeating history: pharmaceuticals in the environment"
623:"Identifying druggable disease-modifying gene products"
931:
Ankley GT, Brooks BW, Huggett DB, Sumpter JP (2007).
263:
Databases containing biological targets information:
669:
454:
429:
448:
423:
151:The term "biological target" is frequently used in
856:
854:
765:
1020:
979:
851:
766:Lomenick B, Olsen RW, Huang J (January 2011).
620:
457:"Chapter 2: How drugs act: general principles"
759:
572:G Protein-Coupled Receptors in Drug Discovery
386:
242:
973:
924:
351:
563:
520:
477:
663:
526:
380:
345:
956:
808:
791:
687:
646:
614:
597:
569:
814:
716:
621:Dixon SJ, Stockwell BR (December 2009).
529:Fundamental & Clinical Pharmacology
289:
1021:
937:Environmental Science & Technology
863:Environmental Science & Technology
722:
982:The Science of the Total Environment
627:Current Opinion in Chemical Biology
13:
14:
1045:
306:, has been shown to increase the
541:10.1111/j.1472-8206.2007.00548.x
1002:10.1016/j.scitotenv.2007.09.008
897:
146:
817:Archives of Pharmacal Research
725:Archives of Pharmacal Research
676:Nature Reviews. Drug Discovery
486:Nature Reviews. Drug Discovery
1:
918:10.1016/S0166-445X(98)00112-X
339:
317:evolutionarily well-conserved
461:Rang and Dale's Pharmacology
432:Rang and Dale's Pharmacology
366:10.1016/0024-3205(89)90182-3
268:Therapeutic Targets Database
258:
72:
7:
580:10.1007/978-1-60327-317-6_4
322:
232:membrane transport proteins
175:G protein-coupled receptors
49:, the receptor target of a
10:
1050:
639:10.1016/j.cbpa.2009.08.003
243:Drug target identification
211:voltage-gated ion channels
829:10.1007/s12272-015-0618-3
737:10.1007/s12272-016-0791-z
218:nuclear hormone receptors
206:ligand-gated ion channels
177:(target of 50% of drugs)
41:pharmacologically active
409:10.1126/science.7939660
77:The external stimulus (
304:17-R-ethinylestradiol
772:ACS Chemical Biology
689:10.1038/nrd.2017.111
290:Conservation ecology
253:forward pharmacology
249:reverse pharmacology
120:ion channel blockade
1034:Biology terminology
994:2008ScTEn.389..329K
949:2007EnST...41.8211A
875:2008EnST...42.5807G
401:1994Sci...266..257M
223:structural proteins
112:receptor antagonism
906:Aquatic Toxicology
312:selective pressure
157:therapeutic effect
958:10.1021/es072658j
883:10.1021/es8005173
869:(15): 5807β5813.
784:10.1021/cb100294v
589:978-1-60327-316-9
470:978-0-7020-3471-8
441:978-0-7020-3471-8
136:enzyme activation
116:enzyme inhibition
21:biological target
1041:
1014:
1013:
977:
971:
970:
960:
928:
922:
921:
901:
895:
894:
858:
849:
848:
812:
806:
805:
795:
763:
757:
756:
720:
714:
713:
691:
667:
661:
660:
650:
618:
612:
611:
601:
567:
561:
560:
524:
518:
517:
481:
475:
474:
452:
446:
445:
427:
421:
420:
384:
378:
377:
349:
132:receptor agonism
1049:
1048:
1044:
1043:
1042:
1040:
1039:
1038:
1019:
1018:
1017:
988:(2β3): 329β39.
978:
974:
929:
925:
902:
898:
859:
852:
813:
809:
764:
760:
731:(9): 1193β201.
721:
717:
668:
664:
633:(5β6): 549β55.
619:
615:
590:
568:
564:
525:
521:
498:10.1038/nrd2199
482:
478:
471:
453:
449:
442:
428:
424:
395:(5183): 257β9.
385:
381:
350:
346:
342:
325:
292:
261:
245:
185:protein kinases
159:or an unwanted
149:
140:inverse agonism
134:(or channel or
75:
17:
12:
11:
5:
1047:
1037:
1036:
1031:
1016:
1015:
972:
943:(24): 8211β7.
923:
912:(2β3): 91β97.
896:
850:
823:(9): 1627β41.
807:
758:
715:
682:(8): 531β543.
662:
613:
588:
562:
519:
476:
469:
447:
440:
422:
379:
343:
341:
338:
337:
336:
331:
329:Drug discovery
324:
321:
300:contraceptives
291:
288:
287:
286:
281:
276:
271:
260:
257:
244:
241:
240:
239:
236:
235:
234:
229:
220:
215:
214:
213:
208:
200:
178:
161:adverse effect
153:pharmaceutical
148:
145:
144:
143:
127:conformational
123:
100:
99:
96:
89:
74:
71:
15:
9:
6:
4:
3:
2:
1046:
1035:
1032:
1030:
1027:
1026:
1024:
1011:
1007:
1003:
999:
995:
991:
987:
983:
976:
968:
964:
959:
954:
950:
946:
942:
938:
934:
927:
919:
915:
911:
907:
900:
892:
888:
884:
880:
876:
872:
868:
864:
857:
855:
846:
842:
838:
834:
830:
826:
822:
818:
811:
803:
799:
794:
789:
785:
781:
777:
773:
769:
762:
754:
750:
746:
742:
738:
734:
730:
726:
719:
712:
707:
703:
699:
695:
690:
685:
681:
677:
673:
666:
658:
654:
649:
644:
640:
636:
632:
628:
624:
617:
609:
605:
600:
595:
591:
585:
581:
577:
573:
566:
558:
554:
550:
546:
542:
538:
534:
530:
523:
515:
511:
507:
503:
499:
495:
492:(12): 993β6.
491:
487:
480:
472:
466:
462:
458:
451:
443:
437:
433:
426:
418:
414:
410:
406:
402:
398:
394:
390:
383:
375:
371:
367:
363:
360:(4): 245β58.
359:
355:
354:Life Sciences
348:
344:
335:
332:
330:
327:
326:
320:
318:
313:
309:
305:
301:
297:
285:
282:
280:
277:
275:
272:
269:
266:
265:
264:
256:
254:
250:
238:nucleic acids
237:
233:
230:
228:
224:
221:
219:
216:
212:
209:
207:
204:
203:
202:ion channels
201:
198:
194:
190:
186:
182:
179:
176:
173:
172:
170:
169:
168:
166:
162:
158:
154:
141:
137:
133:
128:
124:
121:
117:
113:
109:
105:
104:
103:
97:
94:
90:
87:
84:
83:
82:
80:
70:
68:
64:
60:
56:
52:
48:
45:
42:
38:
37:nucleic acids
34:
30:
26:
22:
1029:Pharmacology
985:
981:
975:
940:
936:
926:
909:
905:
899:
866:
862:
820:
816:
810:
778:(1): 34β46.
775:
771:
761:
728:
724:
718:
709:
679:
675:
665:
630:
626:
616:
571:
565:
532:
528:
522:
489:
485:
479:
460:
450:
431:
425:
392:
388:
382:
357:
353:
347:
308:feminization
293:
262:
246:
197:phosphatases
183:(especially
164:
150:
147:Drug targets
101:
78:
76:
63:ion channels
20:
18:
535:(1): 1β18.
165:drug target
91:reversible
86:noncovalent
1023:Categories
340:References
284:Binding DB
108:endogenous
557:205630866
298:in human
259:Databases
193:esterases
189:proteases
171:proteins
73:Mechanism
67:receptors
1010:17936335
967:18200843
891:18754513
837:26040984
802:21077692
753:13577563
745:27387321
698:28685762
657:19740696
608:19513641
549:18251718
514:11979420
506:17139284
323:See also
296:estrogen
279:DrugBank
225:such as
93:covalent
47:compound
33:proteins
990:Bibcode
945:Bibcode
871:Bibcode
845:2399601
793:3031183
706:6180139
648:2787993
599:7122359
417:7939660
397:Bibcode
389:Science
374:2536880
274:DrugMap
227:tubulin
181:enzymes
59:enzymes
55:insulin
51:hormone
1008:
965:
889:
843:
835:
800:
790:
751:
743:
704:
696:
655:
645:
606:
596:
586:
555:
547:
512:
504:
467:
438:
415:
372:
195:, and
65:, and
53:(like
25:ligand
841:S2CID
749:S2CID
702:S2CID
553:S2CID
510:S2CID
270:(TTD)
118:, or
27:or a
1006:PMID
963:PMID
887:PMID
833:PMID
798:PMID
741:PMID
694:PMID
653:PMID
604:PMID
584:ISBN
545:PMID
502:PMID
465:ISBN
436:ISBN
413:PMID
370:PMID
79:i.e.
44:drug
35:and
29:drug
998:doi
986:389
953:doi
914:doi
879:doi
825:doi
788:PMC
780:doi
733:doi
684:doi
643:PMC
635:doi
594:PMC
576:doi
537:doi
494:doi
405:doi
393:266
362:doi
1025::
1004:.
996:.
984:.
961:.
951:.
941:41
939:.
935:.
910:45
908:.
885:.
877:.
867:42
865:.
853:^
839:.
831:.
821:38
819:.
796:.
786:.
774:.
770:.
747:.
739:.
729:39
727:.
708:.
700:.
692:.
680:16
678:.
674:.
651:.
641:.
631:13
629:.
625:.
602:.
592:.
582:.
551:.
543:.
533:22
531:.
508:.
500:.
488:.
459:.
411:.
403:.
391:.
368:.
358:44
356:.
302:,
191:,
187:,
125:A
114:,
69:.
61:,
19:A
1012:.
1000::
992::
969:.
955::
947::
920:.
916::
893:.
881::
873::
847:.
827::
804:.
782::
776:6
755:.
735::
686::
659:.
637::
610:.
578::
559:.
539::
516:.
496::
490:5
473:.
444:.
419:.
407::
399::
376:.
364::
199:)
142:.
122:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.