EM-5854

EM-5854 is a steroidal antiandrogen which was under development by Endoceutics, Inc. (formerly Endorecherche, Inc.) for the treatment of prostate cancer.^{[1][2][3][4][5]} It was first described in a patent in 2008, and was further characterized in 2012.^[2][4] EM-5854 reached phase I/II clinical trials for the treatment of prostate cancer but development was discontinued in March 2019.^[1]

Other names4-Fluoro-17β-hydroxy-17α-[(1-oxidopyridin-1-ium-4-yl)methyl]estra-1,3,5(10)-triene-3-carbonitrile

Drug classSteroidal antiandrogen

CAS Number

• 1071831-57-6 ^Y

PubChem CID

• 25015772

Quick facts Clinical data, Other names ...

EM-5854

Clinical data
Other names	4-Fluoro-17β-hydroxy-17α-[(1-oxidopyridin-1-ium-4-yl)methyl]estra-1,3,5(10)-triene-3-carbonitrile
Drug class	Steroidal antiandrogen
Identifiers
IUPAC name (8R,9S,13S,14S,17R)-4-fluoro-17-hydroxy-13-methyl-17-[(1-oxidopyridin-1-ium-4-yl)methyl]-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3-carbonitrile
CAS Number	1071831-57-6 Y
PubChem CID	25015772
ChemSpider	129562350
CompTox Dashboard (EPA)	DTXSID901336352
Chemical and physical data
Formula	C25H27FN2O2
Molar mass	406.501 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(CC4=CC=[N+](C=C4)[O-])O)CCC5=C3C=CC(=C5F)C#N
InChI InChI=1S/C25H27FN2O2/c1-24-10-6-19-18-3-2-17(15-27)23(26)21(18)5-4-20(19)22(24)7-11-25(24,29)14-16-8-12-28(30)13-9-16/h2-3,8-9,12-13,19-20,22,29H,4-7,10-11,14H2,1H3/t19-,20-,22+,24+,25-/m1/s1 Key:YKLVHERADAJQQV-NGQKKBAQSA-N

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The drug acts as a potent and selective competitive antagonist of the androgen receptor (AR).^[4][5] 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.^[4] 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 RBATooltip relative binding affinity of metribolone, respectively, compared to 0.18% for bicalutamide).^[4][5] They also show dramatically increased antiandrogenic potency relative to bicalutamide in in vivo assays.^[4][5][6] 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.^[4] EM-5854 and EM-5855 show little to no affinity for other steroid hormone receptors including the estrogen, progesterone, and glucocorticoid receptors.^[4] EM-5854 bears a cyano phenyl group, the structural motif of the nonsteroidal antiandrogens.^[7]