17α-Ethynyl-3α-androstanediol explained

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.^{[1] [2] [3]} 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,,,, and, and its mechanism of action is not well-characterized.^[4] 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.^[5]

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).

Notes and References

1. Ahlem C, Kennedy M, Page T, Bell D, Delorme E, Villegas S, Reading C, White S, Stickney D, Frincke J . 17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism . Invest New Drugs . 30 . 1 . 59–78 . 2012 . 20814732 . 10.1007/s10637-010-9517-0 . 24785562 .
2. Trauger R, Corey E, Bell D, White S, Garsd A, Stickney D, Reading C, Frincke J . Inhibition of androstenediol-dependent LNCaP tumour growth by 17alpha-ethynyl-5alpha-androstane-3alpha, 17beta-diol (HE3235) . Br. J. Cancer . 100 . 7 . 1068–72 . 2009 . 19337256 . 2669987 . 10.1038/sj.bjc.6604987 .
3. http://adisinsight.springer.com/drugs/800025305
4. Koreckij TD, Trauger RJ, Montgomery RB, Pitts TE, Coleman I, Nguyen H, Reading CL, Nelson PS, Vessella RL, Corey E . HE3235 inhibits growth of castration-resistant prostate cancer . Neoplasia . 11 . 11 . 1216–25 . 2009 . 19881957 . 2767223 . 10.1593/neo.09960.
5. Beyler AL, Clinton RO . Uterine growth stimulating and testicular growth suppressing activities of 17alpha-ethinylandrostane-3beta, 17beta-diol, its delta 5-analog and derivatives . Proc. Soc. Exp. Biol. Med. . 92 . 2 . 404–8 . June 1956 . 13350363 . 10.3181/00379727-92-22493. 87469965 .