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| Other names | HE-3562; 5α-Dihydro-17α-Ethynyltestosterone; 17α-Ethynyl-DHT; 17α-Ethynyl-5α-androstan-17β-ol-3-one; 5α,17α-Pregn-20-yn-17β-ol-3-one; Ethynylandrostanolone |
| Drug class | Progestin;Progestogen;Androgen;Anabolic steroid |
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| CAS Number | |
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| Chemical and physical data | |
| Formula | C21H30O2 |
| Molar mass | 314.469 g·mol−1 |
| 3D model (JSmol) | |
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5α-Dihydroethisterone (5α-DHET; developmental code nameHE-3562) is anactive metabolite of the formerly clinically used but now-discontinuedprogestinethisterone and the experimental and never-marketedhormonal antineoplastic agentethynylandrostanediol (HE-3235).[1][2] Its formation from its parent drugs iscatalyzed by5α-reductase intissues that express theenzyme in high amounts like theliver,skin,hair follicles, andprostate gland.[1][2][3] 5α-DHET has significantaffinity forsteroid hormone receptors and may contribute importantly to the activities of its parent drugs.[1][2]
Theaffinity of 5α-DHET for theandrogen receptor (AR) is relatively high, in the range of 38 to 100% of that ofdihydrotestosterone (DHT).[1][2][4] A study found that, similarly tonorethisterone and its 5α-reduced metabolite5α-dihydronorethisterone, 5α-DHET showed increased affinity for the AR but decreasedandrogenicpotency relative to ethisterone (Ki = 16.1 nM for 5α-DHET and 101.1 nM for ethisterone, a 6-fold difference in affinity).[1] The decreased androgenic activity of 5α-DHET in spite of increased affinity for the AR relative to ethisterone suggests that it has comparatively reducedefficacy as anagonist of the receptor, analogously toselective androgen receptor modulators (ARpartial agonists) andantiandrogens (ARantagonists).[1] 5α-DHET has relatively low affinity for theprogesterone receptor, only about 12% of that of theprogestogenprogesterone.[2] This is significantly less than that of ethisterone, which has been found to bind to the receptor with an affinity of 35% of that of progesterone.[5][6][7] Conversely, it has relatively high affinity for theglucocorticoid receptor, about 120% of that of thecorticosteroiddexamethasone.[2] In regards to theestrogen receptors, 5α-DHET has weak affinity for theERα of about 3.5% of that ofestradiol, and does not bind to theERβ (Ki > 10 μM).[2]
In addition to steroid hormone receptors, 5α-DHET has very high affinity forsex hormone-binding globulin (Kd = 0.18 nM), anandrogen andestrogenbinding and transport protein that has the effect of intermittently inactivatingsteroid hormones (but also prolonging theirhalf-life in the body).[8][9][10] Its affinity for this protein is among the highest of any known compound and has been found to be roughly equal to that of DHT andmesterolone (1α-methyl-DHT).[8][9][10] This property may contribute to the androgenic activity of 5α-DHET's parent drug ethisterone by displacingendogenous androgens liketestosterone and DHT from SHBG.[11]
Metabolism studies of ethynylandrostanediol revealed that 5α-DHET can be metabolized via C7β and C16αhydroxylation.[2]
5α-DHET, also known as 5α-dihydro-17α-ethynyltestosterone (17α-ethynyl-DHT) as well as 17α-ethynyl-5α-androstan-17β-ol-3-one or 5α,17α-pregn-20-yn-17β-ol-3-one, is asyntheticandrostanesteroid and aderivative oftestosterone.[1][2] It is specifically the combined derivative of5α-dihydrotestosterone (DHT) andethisterone (17α-ethynyltestosterone).[1][2] The steroid is also closely related toethynylandrostanediol (17α-ethynyl-5α-androstane-3α,17β-diol).[2]
Some closely related synthetic 5α-reduced steroid metabolites include5α-dihydronandrolone,5α-dihydronormethandrone,5α-dihydronorethandrolone,5α-dihydronorethisterone, and5α-dihydrolevonorgestrel, as well as19-norandrosterone and19-noretiocholanolone.
Thesteroidal antiandrogenzanoterone (WIN-49596), which was investigated in the 1990s for the treatment ofbenign prostatic hyperplasia but was never marketed, was derived from 5α-DHET.[12][13] In terms ofchemical structure, it is 5α-DHET with apyrazolering-containingmoiety fused at the C2 and C3 positions.[14]
Apartial synthesis of 5α-DHET fromandrostenedione has been published.[15]