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| 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 |
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| CAS Number | |
| PubChemCID | |
| ChemSpider | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C25H27FN2O2 |
| Molar mass | 406.501 g·mol−1 |
| 3D model (JSmol) | |
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EM-5854 is asteroidal antiandrogen which was under development by Endoceutics, Inc. (formerly Endorecherche, Inc.) for the treatment ofprostate cancer.[1][2][3][4][5] It was first described in apatent in 2008, and was further characterized in 2012.[2][4] EM-5854 reachedphase I/IIclinical trials for the treatment of prostate cancer but development was discontinued in March 2019.[1]
The drug acts as apotent andselectivecompetitive antagonist of theandrogen receptor (AR).[4][5] Unlike other steroidal antiandrogens likecyproterone acetate, but similarly tononsteroidal antiandrogens likebicalutamide andenzalutamide, EM-5854 is a pure orsilent antagonist of the AR and shows no intrinsicpartialandrogenic activity.[4] EM-5854 and itsmetaboliteEM-5855 show 3.7-fold and 94-fold higheraffinity for the human AR than bicalutamide (0.66% and 17% of theRBATooltip relative binding affinity ofmetribolone, respectively, compared to 0.18% for bicalutamide).[4][5] They also show dramatically increasedantiandrogenicpotency relative to bicalutamide inin vivoassays.[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 othersteroid hormone receptors including theestrogen,progesterone, andglucocorticoid receptors.[4] EM-5854 bears acyanophenylgroup, thestructural motif of the nonsteroidal antiandrogens.[7]
| Activity | Specifics | BicaTooltip Bicalutamide | FluTooltip Flutamide | OH‑FluTooltip Hydroxyflutamide | EnzaTooltip Enzalutamide | EM‑5854 | EM‑5855 |
|---|---|---|---|---|---|---|---|
| ARTooltip Androgen receptorRBATooltip relative binding affinity (%) | Human | 0.18 | NA | 0.17 | 0.07 | 0.66 | 17 |
| MetriTooltip Metribolone = 100% | Rat | 0.13 | NA | 0.07 | 0.02 | 0.35 | 2.6 |
| Shionogi cellsAATooltip antiandrogenic activity | Ki (nM) | 81 | NA | NA | 170 | 2.0 | 0.77 |
| LNCaP cells (PSATooltip prostate-specific antigen)AA activity andstim of basalprolif | De50 (nM) (Inhib at 10−7 M (%)) | 1750 (6 ± 10) | NA | NA | 1380 (−20 ± 3) | 127 (36 ± 7) | 66 (66 ± 1) |
| Stim at 10−7 M (%) | 0 ± 1 | NA | NA | 1 ± 1 | 19 ± 1 | 29 ± 2 | |
| ERTooltip Estrogen receptorRBATooltip relative binding affinity (%) | Rat (E2 = 100%) | 0 | NA | 0 | 0 | 0 | 0 |
| PRTooltip Progesterone receptorRBATooltip relative binding affinity (%) | Rat (PromTooltip Promegestone = 100%) | ND | NA | 0 | ND | 0.2 | ND |
| GRTooltip Glucocorticoid receptorRBATooltip relative binding affinity (%) | Rat (DexaTooltip Dexamethasone = 100%) | 0 | NA | 0 | <0.1 | 0 | 0 |
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