17α-Ethynyl-3α-androstanediol

{{Short description|Chemical compound}}

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| IUPAC_name = (3R,5S,8R,9S,10S,13S,14S,17R)-17-ethynyl-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthrene-3,17-diol

| image = Ethynylandrostanediol.svg

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| routes_of_administration = By mouth

| class = Estrogen

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| CAS_number = 183387-50-0

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| PubChem = 42611099

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| ChemSpiderID = 32698509

| UNII = 891O182ZP5

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| synonyms = Ethynylandrostanediol; HE3235; Apoptone; 17α-Ethynyl-5α-androstanediol; 17α-Ethynyl-5α-androstane-3α,17β-diol; 5α-Pregn-20-yne-3α,17α-diol

| C=21 | H=32 | O=2

| SMILES = C[C@]12CC[C@H](C[C@@H]1CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC[C@]4(C#C)O)C)O

| StdInChI_Ref =

| StdInChI = 1S/C21H32O2/c1-4-21(23)12-9-18-16-6-5-14-13-15(22)7-10-19(14,2)17(16)8-11-20(18,21)3/h1,14-18,22-23H,5-13H2,2-3H3/t14-,15+,16+,17-,18-,19-,20-,21-/m0/s1

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| StdInChIKey = CKAXZOYFIHQCBN-JRRMKBMNSA-N

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17α-Ethynyl-3α-androstanediol (developmental code names HE-3235, Apoptone), also known as 17α-ethynyl-5α-androstane-3α,17β-diol, is a synthetic androstane steroid and a 17α-substituted derivative of 3α-androstanediol which was never marketed.{{cite journal | vauthors = Ahlem C, Kennedy M, Page T, Bell D, Delorme E, Villegas S, Reading C, White S, Stickney D, Frincke J | title = 17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism | journal = Invest New Drugs | volume = 30 | issue = 1 | pages = 59–78 | year = 2012 | pmid = 20814732 | doi = 10.1007/s10637-010-9517-0 | s2cid = 24785562 }}{{cite journal | vauthors = Trauger R, Corey E, Bell D, White S, Garsd A, Stickney D, Reading C, Frincke J | title = Inhibition of androstenediol-dependent LNCaP tumour growth by 17alpha-ethynyl-5alpha-androstane-3alpha, 17beta-diol (HE3235) | journal = Br. J. Cancer | volume = 100 | issue = 7 | pages = 1068–72 | year = 2009 | pmid = 19337256 | pmc = 2669987 | doi = 10.1038/sj.bjc.6604987 }}[http://adisinsight.springer.com/drugs/800025305 ]{{Dead link|date=January 2022 |bot=InternetArchiveBot |fix-attempted=yes }} It was under development for the treatment of prostate cancer but was discontinued.

17α-Ethynyl-3α-androstanediol itself shows very low affinity for steroid receptors, including the {{abbrlink|AR|androgen receptor}}, {{abbrlink|ERα|estrogen receptor alpha}}, {{abbrlink|ERβ|estrogen receptor beta}}, {{abbrlink|PR|progesterone receptor}}, and {{abbrlink|GR|glucocorticoid receptor}}, and its mechanism of action is not well-characterized.{{cite journal | vauthors = Koreckij TD, Trauger RJ, Montgomery RB, Pitts TE, Coleman I, Nguyen H, Reading CL, Nelson PS, Vessella RL, Corey E | title = HE3235 inhibits growth of castration-resistant prostate cancer | journal = Neoplasia | volume = 11 | issue = 11 | pages = 1216–25 | year = 2009 | pmid = 19881957 | pmc = 2767223 | doi = 10.1593/neo.09960}} It produces 5α-dihydroethisterone (5α-dihydro-17α-ethynyltestosterone), a ligand of several steroid hormone receptors, and 17α-ethynyl-3β-androstanediol, an estrogen, as active metabolites. These metabolites may contribute importantly to the biological activity of 17α-ethynyl-3α-androstanediol, with 17α-ethynyl-3α-androstanediol potentially serving as a prodrug.{{cite journal | vauthors = Beyler AL, Clinton RO | title = Uterine growth stimulating and testicular growth suppressing activities of 17alpha-ethinylandrostane-3beta, 17beta-diol, its delta 5-analog and derivatives | journal = Proc. Soc. Exp. Biol. Med. | volume = 92 | issue = 2 | pages = 404–8 | date = June 1956 | pmid = 13350363 | doi = 10.3181/00379727-92-22493| s2cid = 87469965 }}

{{Affinities of estrogen receptor ligands for the ERα and ERβ}}

Analogues of 17α-ethynyl-3α-androstanediol include 17α-ethynyl-3β-androstanediol, ethinylandrostenediol (17α-ethynyl-5-androstenediol), ethandrostate (17α-ethynyl-5-androstenediol 3β-cyclohexanepropionate), ethinylestradiol (17α-ethynylestradiol), ethisterone (17α-ethynyltestosterone), and 5α-dihydroethisterone (17α-ethynyldihydrotestosterone).