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Chemical compound
Pharmaceutical compound
SB-236057
Clinical data
Other namesSB236057; SB-236057-A; SB-236057A; SB236057A
Routes of
administration
Oral
Drug classSerotonin 5-HT1B receptor inverse agonist
ATC code
  • None
Identifiers
  • 1'-ethyl-5-[2'-methyl-4'-(5-methyl-1,3,4-oxadiazolyl-2-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro(furo[2,3-f]indole-3,4'-piperidine)
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC33H34N4O3
Molar mass534.660 g·mol−1
3D model (JSmol)
  • n5nc(C)oc5-c(cc2C)ccc2-c6ccc(cc6)C(=O)N(CCc1cc3OC7)c1cc3C7(CC4)CCN4CC
  • InChI=1S/C33H34N4O3/c1-4-36-15-12-33(13-16-36)20-39-30-18-25-11-14-37(29(25)19-28(30)33)32(38)24-7-5-23(6-8-24)27-10-9-26(17-21(27)2)31-35-34-22(3)40-31/h5-10,17-19H,4,11-16,20H2,1-3H3
  • Key:WXAKEEQOWUHGCI-UHFFFAOYSA-N

SB-236057 is a compound which is a potent and selective inverse agonist for the serotonin receptor 5-HT1B, acting especially at 5-HT1B autoreceptors on nerve terminals. It produces a rapid increase in serotonin levels in the brain, and was originally researched as a potential antidepressant.[2][3] However subsequent research found that SB-236,057 also acts as a potent teratogen, producing severe musculoskeletal birth defects when rodents were exposed to it during pregnancy. This has made it of little use for research into its original applications, yet has made it useful for studying embryonic development instead.[4][5] The drug was under development by GlaxoSmithKline for the treatment of major depressive disorder in the 2000s and reached the preclinical research stage of development but was never marketed.

See also

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References

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  1. Middlemiss DN, Göthert M, Schlicker E, Scott CM, Selkirk JV, Watson J, et al. (June 1999). "SB-236057, a selective 5-HT1B receptor inverse agonist, blocks the 5-HT human terminal autoreceptor". European Journal of Pharmacology. 375 (1–3): 359–65. doi:10.1016/s0014-2999(99)00262-9. PMID 10443589.
  2. Roberts C, Watson J, Price GW, Middlemiss DN (2006). "SB-236057-A: a selective 5-HT1B receptor inverse agonist". CNS Drug Reviews. 7 (4): 433–44. doi:10.1111/j.1527-3458.2001.tb00209.x. PMC 6741665. PMID 11830759.
  3. Augustine-Rauch KA, Zhang QJ, Posobiec L, Mirabile R, DeBoer LS, Solomon HM, Wier PJ (October 2004). "SB-236057: Critical window of sensitivity study and embryopathy of a potent musculoskeletal teratogen". Birth Defects Research. Part A, Clinical and Molecular Teratology. 70 (10): 773–88. doi:10.1002/bdra.20079. PMID 15472921.