|Drug class||Steroidal antiandrogen|
|Chemical and physical data|
|Molar mass||406.501 g·mol−1|
|3D model (JSmol)|
EM-5854 is a steroidal antiandrogen which was under development by Endoceutics, Inc. (formerly Endorecherche, Inc.) for the treatment of prostate cancer. It was first described in a patent in 2008, and was further characterized in 2012. EM-5854 reached phase I/II clinical trials for the treatment of prostate cancer but development was discontinued in March 2019.
The drug acts as a potent and selective competitive antagonist of the androgen receptor (AR). Unlike other steroidal antiandrogens like cyproterone acetate, but similarly to nonsteroidal antiandrogens like bicalutamide and enzalutamide, EM-5854 is a pure or silent antagonist of the AR and shows no intrinsic partial androgenic activity. EM-5854 and its metabolite EM-5855 show 3.7-fold and 94-fold higher affinity for the human AR than bicalutamide (0.66% and 17% of the RBA of metribolone, respectively, compared to 0.18% for bicalutamide). They also show dramatically increased antiandrogenic potency relative to bicalutamide in in vivo assays. On the basis of the available research, it has been said that EM-5854 may possibly have 70- to 140-fold the antiandrogenic potency of bicalutamide in humans. EM-5854 and EM-5855 show little to no affinity for other steroid hormone receptors including the estrogen, progesterone, and glucocorticoid receptors. EM-5854 bears a cyanophenyl group, the structural motif of the nonsteroidal antiandrogens.
|AR RBA (%)||Human||0.18||NA||0.17||0.07||0.66||17|
|Metri = 100%||Rat||0.13||NA||0.07||0.02||0.35||2.6|
|Shionogi cells AA activity||Ki (nM)||81||NA||NA||170||2.0||0.77|
|LNCaP cells (PSA) AA activity and stim of basal prolif||De50 (nM) (Inhib at 10−7 M (%))||1750
(6 ± 10)
(−20 ± 3)
(36 ± 7)
(66 ± 1)
|Stim at 10−7 M (%)||0 ± 1||NA||NA||1 ± 1||19 ± 1||29 ± 2|
|ER RBA (%)||Rat (E2 = 100%)||0||NA||0||0||0||0|
|PR RBA (%)||Rat (Prom = 100%)||ND||NA||0||ND||0.2||ND|
|GR RBA (%)||Rat (Dexa = 100%)||0||NA||0||<0.1||0||0|
- "EM 5854 - AdisInsight".
- Endorecherche, Inc. Preparation of 17α-substituted steroids as systemic antiandrogens and selective androgen receptor modulators. WO2008124922; 2008 https://patents.google.com/patent/US9284345B2/en
- Zhang X, Lanter JC, Sui Z (September 2009). "Recent advances in the development of selective androgen receptor modulators". Expert Opin Ther Pat. 19 (9): 1239–58. doi:10.1517/13543770902994397. PMID 19505196.
- Gauthier S, Martel C, Labrie F (October 2012). "Steroid derivatives as pure antagonists of the androgen receptor". J. Steroid Biochem. Mol. Biol. 132 (1–2): 93–104. doi:10.1016/j.jsbmb.2012.02.006. PMID 22449547.
- Cabeza M, Sánchez-Márquez A, Garrido M, Silva A, Bratoeff E (2016). "Recent Advances in Drug Design and Drug Discovery for Androgen- Dependent Diseases". Curr. Med. Chem. 23 (8): 792–815. doi:10.2174/0929867323666160210125642. PMC 5412001. PMID 26861003.
- Salvador JA, Carvalho JF, Neves MA, Silvestre SM, Leitão AJ, Silva MM, Sá e Melo ML (February 2013). "Anticancer steroids: linking natural and semi-synthetic compounds". Nat Prod Rep. 30 (2): 324–74. doi:10.1039/c2np20082a. PMID 23151898.
- Fujii S, Kagechika H (June 2019). "Androgen receptor modulators: a review of recent patents and reports (2012-2018)". Expert Opin Ther Pat. 29 (6): 439–453. doi:10.1080/13543776.2019.1618831. PMID 31092069.
- EM-5854 - AdisInsight
- Research programme: androgen receptor antagonists (EM-4350, EM-5855, EM-6537) - AdisInsight
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