Английская Википедия:EM-5854
Шаблон:Short description Шаблон:Drugbox
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]
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 Шаблон:Abbrlink 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]
| Activity | Specifics | Шаблон:Abbrlink | Шаблон:Abbrlink | Шаблон:Abbrlink | Шаблон:Abbrlink | EM‑5854 | EM‑5855 |
|---|---|---|---|---|---|---|---|
| Шаблон:Abbrlink Шаблон:Abbrlink (%) | Human | 0.18 | Шаблон:Abbr | 0.17 | 0.07 | 0.66 | 17 |
| Шаблон:Abbrlink = 100% | Rat | 0.13 | Шаблон:Abbr | 0.07 | 0.02 | 0.35 | 2.6 |
| Shionogi cells Шаблон:Abbrlink activity | Ki (nM) | 81 | Шаблон:Abbr | Шаблон:Abbr | 170 | 2.0 | 0.77 |
| LNCaP cells (Шаблон:Abbrlink) Шаблон:Abbr activity and Шаблон:Abbr of basal Шаблон:Abbr | [[Effective dose (pharmacology)|Шаблон:Abbr (nM)]] (Шаблон:Abbr at 10Шаблон:Sup M (%)) | 1750 (6 ± 10) |
Шаблон:Abbr | Шаблон:Abbr | 1380 (−20 ± 3) |
127 (36 ± 7) |
66 (66 ± 1) |
| Шаблон:Abbr at 10Шаблон:Sup M (%) | 0 ± 1 | Шаблон:Abbr | Шаблон:Abbr | 1 ± 1 | 19 ± 1 | 29 ± 2 | |
| Шаблон:Abbrlink Шаблон:Abbrlink (%) | Rat ([[Estradiol (medication)|Шаблон:Abbr]] = 100%) | 0 | Шаблон:Abbr | 0 | 0 | 0 | 0 |
| Шаблон:Abbrlink Шаблон:Abbrlink (%) | Rat (Шаблон:Abbrlink = 100%) | Шаблон:Abbr | Шаблон:Abbr | 0 | Шаблон:Abbr | 0.2 | ND |
| Шаблон:Abbrlink Шаблон:Abbrlink (%) | Rat (Шаблон:Abbrlink = 100%) | 0 | Шаблон:Abbr | 0 | <0.1 | 0 | 0 |
References
External links
- EM-5854 - AdisInsight
- Research programme: androgen receptor antagonists (EM-4350, EM-5855, EM-6537) - AdisInsight
Шаблон:Androgen receptor modulators
Шаблон:Genito-urinary-drug-stub
Шаблон:Antineoplastic-drug-stub
- ↑ 1,0 1,1 Шаблон:Cite web
- ↑ 2,0 2,1 Endorecherche, Inc. Preparation of 17α-substituted steroids as systemic antiandrogens and selective androgen receptor modulators. WO2008124922; 2008 https://patents.google.com/patent/US9284345B2/en
- ↑ Шаблон:Cite journal
- ↑ 4,0 4,1 4,2 4,3 4,4 4,5 4,6 4,7 4,8 Шаблон:Cite journal
- ↑ 5,0 5,1 5,2 5,3 Шаблон:Cite journal
- ↑ Шаблон:Cite journal
- ↑ Шаблон:Cite journal
- Английская Википедия
- Abandoned drugs
- Tertiary alcohols
- Estranes
- Experimental cancer drugs
- Fluoroarenes
- Hormonal antineoplastic drugs
- Nitriles
- Prostate cancer
- Pyridinium compounds
- Steroidal antiandrogens
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