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| Other names | TMT; R-2956; RU-2956; 2α,2β,17α-Trimethyltrienolone; 2α,2β,17α-Trimethyltrenbolone; 2α,2β-Dimethylmetribolone; δ9,11-2α,2β,17α-trimethyl-19-nortestosterone; 2α,2β,17α-Trimethylestra-4,9,11-trien-17β-ol-3-one; 17β-Hydroxy-2α,2β,17α-trimethylestra-4,9,11-trien-3-one |
| Drug class | Steroidal antiandrogen |
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| Chemical and physical data | |
| Formula | C21H28O2 |
| Molar mass | 312.453 g·mol−1 |
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Trimethyltrienolone (TMT), also known by its developmental code nameR-2956 orRU-2956, is anantiandrogen medication which was never introduced for medical use but has been used inscientific research.[1][2][3]
Due to its close relation tometribolone (methyltrienolone), it is thought that TMT may producehepatotoxicity.[4]
TMT is aselective and highlypotentcompetitiveantagonist of theandrogen receptor (AR) with very lowintrinsic/partialandrogenic activity and noestrogenic,antiestrogenic,progestogenic, orantimineralocorticoid activity.[5][6] The drug is aderivative of the extremely potentandrogen/anabolic steroidmetribolone (R-1881; 17α-methyltrenbolone),[6][7] and has been reported to possess only about 4-fold loweraffinity for the AR in comparison.[8] In accordance, it has relatively high affinity for the AR among steroidal antiandrogens, and almost completely inhibitsdihydrotestosterone (DHT) binding to the ARin vitro at a mere 10-fold molar excess.[9] The AR weak partial agonistic activity of TMT is comparable to that ofcyproterone acetate.[4]
| Compound | PRTooltip Progesterone receptor | ARTooltip Androgen receptor | ERTooltip Estrogen receptor | GRTooltip Glucocorticoid receptor | MRTooltip Mineralocorticoid receptor |
|---|---|---|---|---|---|
| Testosterone | 1–3, 1–5 | 100 | <1 | <1, 1–5 | <1 |
| 5α-Dihydrotestosterone | <1, 1–3 | 100–125 | <1 | <1 | <1 |
| Metribolone (RU-1881) | 200–300, 250–600 | 200–300, 250–600 | <1 | 25–50 | 15–25 |
| Trimethyltrienolone (RU-2956) | ≤1 | 14 | <1 | <1 | <1 |
| Notes: Values are percentages (%). Referenceligands (100%) wereprogesterone for thePRTooltip progesterone receptor,testosterone for theARTooltip androgen receptor,E2 for theERTooltip estrogen receptor,DEXATooltip dexamethasone for theGRTooltip glucocorticoid receptor, andaldosterone for theMRTooltip mineralocorticoid receptor.Sources:[10][11][12][13][6] | |||||
TMT, also known as 2α,2β,17α-trimethyltrienolone[14] or as δ9,11-2α,2β,17α-trimethyl-19-nortestosterone, as well as 2α,2β,17α-trimethylestra-4,9,11-trien-17β-ol-3-one, is asyntheticestranesteroid and aderivative oftestosterone and19-nortestosterone.[5][15][2] It is the 2α,2β,17α-trimethyl derivative oftrenbolone (trienolone) and the 2α,2β-dimethyl derivative ofmetribolone (methyltrienolone), both of which are syntheticandrogens/anabolic steroids.[15]
TMT was developed byRoussel Uclaf inFrance and was first known as early as 1969.[3][16][15] It was one of the earliest antiandrogens to be discovered and developed, along with others such asbenorterone,BOMT,cyproterone, andcyproterone acetate.[5][17][18][19][20] The drug was under investigation by Roussel Uclaf for potential medical use, but was abandoned in favor ofnonsteroidal antiandrogens likeflutamide andnilutamide due to their comparative advantage of a complete lack of androgenicity.[1] Roussel Uclaf subsequently developed and introduced nilutamide for medical use.[21]
[...] flutamide but we soon abandoned the development of steroid derivatives such as RU 2956 because of inherent androgenicity [17], and focused on the nonsteroidal antiandrogens.
10635 (8596) C21H28O2 23983-19-9 17β-Hydroxy-2,2,17-trimethylestra-4,9,11-trien-3-one : (17β)-17-Hydroxy-2,2,17-trimethylestra-4,9,11-trien-3-one (•) S R 2956 U Anti-androgen
R 2956 (17beta-hydroxy-2,2,17-trimethyl-estra-4,9,11-trien-3-one) was tested for antiandrogenic activity in rats (Dorfman test); in dogs; for androgenic activity in female rats (Hershberger); in male rats; for progestagenic activity in rabbits (Clauberg); for uterotrophic activity in mice (Rubin); and for antiestrogenic activity in mice (Dorfman). R 2956 significantly antagonized the hypertrophic effect of .05 mg testosterone propionate on rat seminal vesicles and ventral prostate in proportion to dose from .4-5 mg/day orally. In dogs R 2956 lowered prostate epithelial hyperplasia induced by androstanolone. R 2956 had no androgenic, estrogenic, progestational, or antiestrogenic activities and inhibited development of corpora lutea to an extent comparable with that of norethindrone.
R-2956 [41-43], a dimethyl derivative of an extremely potent androgen, R 1881 [44], is a powerful testosterone antagonist with very low androgenic activity.
At this stage, RU 2956 exerts a competitive effect about 4 times less marked than metribolone may be because the steric hindrance of the dimethyl group in position C-2 interferes with H-bond formation between the C-3 oxygen and the receptor protein, i.e., with the recognition step, and consequently, with the association rate.
Administration of steroidal, blocking agents such as spironolactone, cyproterone acetate, or trimethyltrienolone, or nonsteroidal, such as flutamide, bicalutamide, blocking agents, can attain this result (169–171).
Several androstane derivatives have also demonstrated an antiandrogenic activity; 17a-methyl-B-nortestosterone 8 was prepared and tested in 1964 for antihormonal activity [43]. Within the next decade, several other androstane analogs were prepared and found to possess antiandrogenic activity [43, 44, 45, 46] including BOMT 9 "figure 2", R2956 10, SC9420 11, and oxendolone 12 "figure 3".
