EM-5854 is a steroidal antiandrogen which was under development by Endoceutics, Inc. (formerly Endorecherche, Inc.) for the treatment of prostate cancer.Endorecherche, Inc. Preparation of 17α-substituted steroids as systemic antiandrogens and selective androgen receptor modulators. WO2008124922; 2008 https://patents.google.com/patent/US9284345B2/en 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 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 cyano phenyl group, the structural motif of the nonsteroidal antiandrogens.
EM-5854 and other AR antagonists at steroid hormone receptors and in AR-dependent cancer cell lines Activity Specifics EM‑5854 EM‑5855 (%) Human 0.18 0.17 0.07 0.66 17 = 100% Rat 0.13 0.07 0.02 0.35 2.6 Shionogi cells activity Ki (nM) 81 170 2.0 0.77 LNCaP cells () activity and of basal (nM) ( at 10 M (%)) 1750(6 ± 10) 1380(−20 ± 3) 127(36 ± 7) 66(66 ± 1) at 10 M (%) 0 ± 1 1 ± 1 19 ± 1 29 ± 2 (%) Rat ( = 100%) 0 0 0 0 0 (%) Rat ( = 100%) 0 0.2 ND (%) Rat ( = 100%) 0 0 <0.1 0 0
References
External links EM-5854 - AdisInsight Research programme: androgen receptor antagonists (EM-4350, EM-5855, EM-6537) - AdisInsight