BMS-641988

BMS-641988
INN
Drug class	Nonsteroidal antiandrogen
Routes of administration	By mouth
Pregnancy category
Bioavailability
Metabolism
Elimination half-life
Excretion
Legal status
CAS Number	1093276-09-5
PubChem	24768935
DrugBank
ChemSpider
KEGG

BMS-641988 is a nonsteroidal antiandrogen which was developed by Bristol-Myers Squibb for the treatment of prostate cancer but was never marketed.<ref name="AdisInsight">https://adisinsight.springer.com/drugs/800026026</ref><ref name="pmid19654297">,

 Discovery of BMS-641988, a novel and potent inhibitor of androgen receptor signaling for the treatment of prostate cancer, 
 Cancer Res., 
 
 Vol. 69(Issue: 16),
 pp. 6522–30,
 DOI: 10.1158/0008-5472.CAN-09-1111,
 PMID: 19654297,</ref><ref name="pmid26861003">, 
 Recent Advances in Drug Design and Drug Discovery for Androgen- Dependent Diseases, 
 Curr. Med. Chem., 
 
 Vol. 23(Issue: 8),
 pp. 792–815,
 DOI: 10.2174/0929867323666160210125642,
 PMID: 26861003,
 PMC: 5412001,
 
 Full text,</ref> It acts as a potent competitive antagonist of the androgen receptor (AR) (Ki = 10 nM; IC50


= 56 nM).<ref name="pmid26861003" /> The drug was found to have 20-fold higher affinity for the AR than bicalutamide in MDA-MB-453 cells, and showed 3- to 7-fold the antiandrogenic activity of bicalutamide in vitro.<ref name="pmid21426013">, 
 Novel, potent anti-androgens of therapeutic potential: recent advances and promising developments, 
 Future Med Chem, 
 
 Vol. 2(Issue: 4),
 pp. 667–80,
 DOI: 10.4155/fmc.10.14,
 PMID: 21426013,</ref> It may have some weak partial agonist activity at the androgen receptor.<ref name="pmid21426013" /> BMS-641988 is transformed by CYP3A4 into BMS-570511, and this metabolite is then reduced to BMS-501949 by cytosolic reductases.<ref name="pmid21131556">, 
 Phase I dose-escalation study of the novel antiandrogen BMS-641988 in patients with castration-resistant prostate cancer, 
 Clin. Cancer Res., 
 
 Vol. 17(Issue: 4),
 pp. 880–7,
 DOI: 10.1158/1078-0432.CCR-10-2955,
 PMID: 21131556,
 PMC: 3070382,</ref><ref name="pmid21426013" /> All three compounds show similar antiandrogenic activity.<ref name="pmid21131556" /> In addition to its antiandrogenic activity, BMS-641988 shows activity as a negative allosteric modulator of the GABAA receptor, and can produce seizures in animals at sufficiently high doses.<ref name="BarrishCarter2010">, 
  
 Accounts in Drug Discovery: Case Studies in Medicinal Chemistry. online version, 
  
 Royal Society of Chemistry, 
  
  
  
 ISBN 978-1-84973-198-0, 
  
  
  
 Pages: 120–,</ref> It also shows some drug-induced QT prolongation.<ref name="BarrishCarter2010" /> BMS-641988 reached phase I clinical trials prior to the discontinuation of its development.<ref name="AdisInsight" /> The clinical development of BMS-641988 was terminated due to the occurrence of a seizure in a patient during a phase I study.<ref name="pmid21131556" />

External links

• BMS-641988 - AdisInsight

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