Ethandrostate
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Clinical data | |
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Other names | Ethynylandrostenediol 3β-cyclohexanepropionate; 17α-Ethynylandrost-5-ene-3β,17β-diol 3β-cyclohexanepropionate; 17α-Pregn-5-en-20-yne-3β,17β-diol 3β-cyclohexanepropionate; NSC-18216 |
Routes of administration | By mouth, intramuscular injection |
Drug class | Estrogen |
Identifiers | |
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PubChem CID | |
ChemSpider | |
Chemical and physical data | |
Formula | C30H44O3 |
Molar mass | 452.679 g·mol−1 |
3D model (JSmol) | |
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Ethandrostate, also known as ethinylandrostenediol 3β-cyclohexanepropionate, is a synthetic steroidal estrogen and ester of ethinylandrostenediol (17α-ethynyl-5-androstenediol) which was developed and studied in people with certain cancers like breast cancer and prostate cancer in the 1950s but was never marketed.[1][2][3][4] Although far less potent by weight than estradiol or estrone, ethandrostate produces estrogenic effects in the vagina, uterus, and mammary glands as well as antigonadotropic and secondary antiandrogenic effects like testicular and prostate atrophy in both animals and humans.[1][3][4] Ethandrostate was assessed in humans as an aqueous suspension by intramuscular injection at doses of 100 to 200 mg/day or 100 mg three times per week and by mouth at a dose of 25 mg four times per day.[4] It shows much greater antigonadotropic potency relative to general estrogenic potency in animals when compared with other estrogens.[3] However, this doesn't seem to be the case in humans.[4] In addition to its estrogenic activity, ethandrostate has very weak androgenic activity that manifests only at doses much higher than its estrogenic activity.[3]
Ligand | Other names | Relative binding affinities (RBA, %)a | Absolute binding affinities (Ki, nM)a | Action | ||
---|---|---|---|---|---|---|
ERα | ERβ | ERα | ERβ | |||
Estradiol | E2; 17β-Estradiol | 100 | 100 | 0.115 (0.04–0.24) | 0.15 (0.10–2.08) | Estrogen |
Estrone | E1; 17-Ketoestradiol | 16.39 (0.7–60) | 6.5 (1.36–52) | 0.445 (0.3–1.01) | 1.75 (0.35–9.24) | Estrogen |
Estriol | E3; 16α-OH-17β-E2 | 12.65 (4.03–56) | 26 (14.0–44.6) | 0.45 (0.35–1.4) | 0.7 (0.63–0.7) | Estrogen |
Estetrol | E4; 15α,16α-Di-OH-17β-E2 | 4.0 | 3.0 | 4.9 | 19 | Estrogen |
Alfatradiol | 17α-Estradiol | 20.5 (7–80.1) | 8.195 (2–42) | 0.2–0.52 | 0.43–1.2 | Metabolite |
16-Epiestriol | 16β-Hydroxy-17β-estradiol | 7.795 (4.94–63) | 50 | ? | ? | Metabolite |
17-Epiestriol | 16α-Hydroxy-17α-estradiol | 55.45 (29–103) | 79–80 | ? | ? | Metabolite |
16,17-Epiestriol | 16β-Hydroxy-17α-estradiol | 1.0 | 13 | ? | ? | Metabolite |
2-Hydroxyestradiol | 2-OH-E2 | 22 (7–81) | 11–35 | 2.5 | 1.3 | Metabolite |
2-Methoxyestradiol | 2-MeO-E2 | 0.0027–2.0 | 1.0 | ? | ? | Metabolite |
4-Hydroxyestradiol | 4-OH-E2 | 13 (8–70) | 7–56 | 1.0 | 1.9 | Metabolite |
4-Methoxyestradiol | 4-MeO-E2 | 2.0 | 1.0 | ? | ? | Metabolite |
2-Hydroxyestrone | 2-OH-E1 | 2.0–4.0 | 0.2–0.4 | ? | ? | Metabolite |
2-Methoxyestrone | 2-MeO-E1 | <0.001–<1 | <1 | ? | ? | Metabolite |
4-Hydroxyestrone | 4-OH-E1 | 1.0–2.0 | 1.0 | ? | ? | Metabolite |
4-Methoxyestrone | 4-MeO-E1 | <1 | <1 | ? | ? | Metabolite |
16α-Hydroxyestrone | 16α-OH-E1; 17-Ketoestriol | 2.0–6.5 | 35 | ? | ? | Metabolite |
2-Hydroxyestriol | 2-OH-E3 | 2.0 | 1.0 | ? | ? | Metabolite |
4-Methoxyestriol | 4-MeO-E3 | 1.0 | 1.0 | ? | ? | Metabolite |
Estradiol sulfate | E2S; Estradiol 3-sulfate | <1 | <1 | ? | ? | Metabolite |
Estradiol disulfate | Estradiol 3,17β-disulfate | 0.0004 | ? | ? | ? | Metabolite |
Estradiol 3-glucuronide | E2-3G | 0.0079 | ? | ? | ? | Metabolite |
Estradiol 17β-glucuronide | E2-17G | 0.0015 | ? | ? | ? | Metabolite |
Estradiol 3-gluc. 17β-sulfate | E2-3G-17S | 0.0001 | ? | ? | ? | Metabolite |
Estrone sulfate | E1S; Estrone 3-sulfate | <1 | <1 | >10 | >10 | Metabolite |
Estradiol benzoate | EB; Estradiol 3-benzoate | 10 | ? | ? | ? | Estrogen |
Estradiol 17β-benzoate | E2-17B | 11.3 | 32.6 | ? | ? | Estrogen |
Estrone methyl ether | Estrone 3-methyl ether | 0.145 | ? | ? | ? | Estrogen |
ent-Estradiol | 1-Estradiol | 1.31–12.34 | 9.44–80.07 | ? | ? | Estrogen |
Equilin | 7-Dehydroestrone | 13 (4.0–28.9) | 13.0–49 | 0.79 | 0.36 | Estrogen |
Equilenin | 6,8-Didehydroestrone | 2.0–15 | 7.0–20 | 0.64 | 0.62 | Estrogen |
17β-Dihydroequilin | 7-Dehydro-17β-estradiol | 7.9–113 | 7.9–108 | 0.09 | 0.17 | Estrogen |
17α-Dihydroequilin | 7-Dehydro-17α-estradiol | 18.6 (18–41) | 14–32 | 0.24 | 0.57 | Estrogen |
17β-Dihydroequilenin | 6,8-Didehydro-17β-estradiol | 35–68 | 90–100 | 0.15 | 0.20 | Estrogen |
17α-Dihydroequilenin | 6,8-Didehydro-17α-estradiol | 20 | 49 | 0.50 | 0.37 | Estrogen |
Δ8-Estradiol | 8,9-Dehydro-17β-estradiol | 68 | 72 | 0.15 | 0.25 | Estrogen |
Δ8-Estrone | 8,9-Dehydroestrone | 19 | 32 | 0.52 | 0.57 | Estrogen |
Ethinylestradiol | EE; 17α-Ethynyl-17β-E2 | 120.9 (68.8–480) | 44.4 (2.0–144) | 0.02–0.05 | 0.29–0.81 | Estrogen |
Mestranol | EE 3-methyl ether | ? | 2.5 | ? | ? | Estrogen |
Moxestrol | RU-2858; 11β-Methoxy-EE | 35–43 | 5–20 | 0.5 | 2.6 | Estrogen |
Methylestradiol | 17α-Methyl-17β-estradiol | 70 | 44 | ? | ? | Estrogen |
Diethylstilbestrol | DES; Stilbestrol | 129.5 (89.1–468) | 219.63 (61.2–295) | 0.04 | 0.05 | Estrogen |
Hexestrol | Dihydrodiethylstilbestrol | 153.6 (31–302) | 60–234 | 0.06 | 0.06 | Estrogen |
Dienestrol | Dehydrostilbestrol | 37 (20.4–223) | 56–404 | 0.05 | 0.03 | Estrogen |
Benzestrol (B2) | – | 114 | ? | ? | ? | Estrogen |
Chlorotrianisene | TACE | 1.74 | ? | 15.30 | ? | Estrogen |
Triphenylethylene | TPE | 0.074 | ? | ? | ? | Estrogen |
Triphenylbromoethylene | TPBE | 2.69 | ? | ? | ? | Estrogen |
Tamoxifen | ICI-46,474 | 3 (0.1–47) | 3.33 (0.28–6) | 3.4–9.69 | 2.5 | SERM |
Afimoxifene | 4-Hydroxytamoxifen; 4-OHT | 100.1 (1.7–257) | 10 (0.98–339) | 2.3 (0.1–3.61) | 0.04–4.8 | SERM |
Toremifene | 4-Chlorotamoxifen; 4-CT | ? | ? | 7.14–20.3 | 15.4 | SERM |
Clomifene | MRL-41 | 25 (19.2–37.2) | 12 | 0.9 | 1.2 | SERM |
Cyclofenil | F-6066; Sexovid | 151–152 | 243 | ? | ? | SERM |
Nafoxidine | U-11,000A | 30.9–44 | 16 | 0.3 | 0.8 | SERM |
Raloxifene | – | 41.2 (7.8–69) | 5.34 (0.54–16) | 0.188–0.52 | 20.2 | SERM |
Arzoxifene | LY-353,381 | ? | ? | 0.179 | ? | SERM |
Lasofoxifene | CP-336,156 | 10.2–166 | 19.0 | 0.229 | ? | SERM |
Ormeloxifene | Centchroman | ? | ? | 0.313 | ? | SERM |
Levormeloxifene | 6720-CDRI; NNC-460,020 | 1.55 | 1.88 | ? | ? | SERM |
Ospemifene | Deaminohydroxytoremifene | 0.82–2.63 | 0.59–1.22 | ? | ? | SERM |
Bazedoxifene | – | ? | ? | 0.053 | ? | SERM |
Etacstil | GW-5638 | 4.30 | 11.5 | ? | ? | SERM |
ICI-164,384 | – | 63.5 (3.70–97.7) | 166 | 0.2 | 0.08 | Antiestrogen |
Fulvestrant | ICI-182,780 | 43.5 (9.4–325) | 21.65 (2.05–40.5) | 0.42 | 1.3 | Antiestrogen |
Propylpyrazoletriol | PPT | 49 (10.0–89.1) | 0.12 | 0.40 | 92.8 | ERα agonist |
16α-LE2 | 16α-Lactone-17β-estradiol | 14.6–57 | 0.089 | 0.27 | 131 | ERα agonist |
16α-Iodo-E2 | 16α-Iodo-17β-estradiol | 30.2 | 2.30 | ? | ? | ERα agonist |
Methylpiperidinopyrazole | MPP | 11 | 0.05 | ? | ? | ERα antagonist |
Diarylpropionitrile | DPN | 0.12–0.25 | 6.6–18 | 32.4 | 1.7 | ERβ agonist |
8β-VE2 | 8β-Vinyl-17β-estradiol | 0.35 | 22.0–83 | 12.9 | 0.50 | ERβ agonist |
Prinaberel | ERB-041; WAY-202,041 | 0.27 | 67–72 | ? | ? | ERβ agonist |
ERB-196 | WAY-202,196 | ? | 180 | ? | ? | ERβ agonist |
Erteberel | SERBA-1; LY-500,307 | ? | ? | 2.68 | 0.19 | ERβ agonist |
SERBA-2 | – | ? | ? | 14.5 | 1.54 | ERβ agonist |
Coumestrol | – | 9.225 (0.0117–94) | 64.125 (0.41–185) | 0.14–80.0 | 0.07–27.0 | Xenoestrogen |
Genistein | – | 0.445 (0.0012–16) | 33.42 (0.86–87) | 2.6–126 | 0.3–12.8 | Xenoestrogen |
Equol | – | 0.2–0.287 | 0.85 (0.10–2.85) | ? | ? | Xenoestrogen |
Daidzein | – | 0.07 (0.0018–9.3) | 0.7865 (0.04–17.1) | 2.0 | 85.3 | Xenoestrogen |
Biochanin A | – | 0.04 (0.022–0.15) | 0.6225 (0.010–1.2) | 174 | 8.9 | Xenoestrogen |
Kaempferol | – | 0.07 (0.029–0.10) | 2.2 (0.002–3.00) | ? | ? | Xenoestrogen |
Naringenin | – | 0.0054 (<0.001–0.01) | 0.15 (0.11–0.33) | ? | ? | Xenoestrogen |
8-Prenylnaringenin | 8-PN | 4.4 | ? | ? | ? | Xenoestrogen |
Quercetin | – | <0.001–0.01 | 0.002–0.040 | ? | ? | Xenoestrogen |
Ipriflavone | – | <0.01 | <0.01 | ? | ? | Xenoestrogen |
Miroestrol | – | 0.39 | ? | ? | ? | Xenoestrogen |
Deoxymiroestrol | – | 2.0 | ? | ? | ? | Xenoestrogen |
β-Sitosterol | – | <0.001–0.0875 | <0.001–0.016 | ? | ? | Xenoestrogen |
Resveratrol | – | <0.001–0.0032 | ? | ? | ? | Xenoestrogen |
α-Zearalenol | – | 48 (13–52.5) | ? | ? | ? | Xenoestrogen |
β-Zearalenol | – | 0.6 (0.032–13) | ? | ? | ? | Xenoestrogen |
Zeranol | α-Zearalanol | 48–111 | ? | ? | ? | Xenoestrogen |
Taleranol | β-Zearalanol | 16 (13–17.8) | 14 | 0.8 | 0.9 | Xenoestrogen |
Zearalenone | ZEN | 7.68 (2.04–28) | 9.45 (2.43–31.5) | ? | ? | Xenoestrogen |
Zearalanone | ZAN | 0.51 | ? | ? | ? | Xenoestrogen |
Bisphenol A | BPA | 0.0315 (0.008–1.0) | 0.135 (0.002–4.23) | 195 | 35 | Xenoestrogen |
Endosulfan | EDS | <0.001–<0.01 | <0.01 | ? | ? | Xenoestrogen |
Kepone | Chlordecone | 0.0069–0.2 | ? | ? | ? | Xenoestrogen |
o,p'-DDT | – | 0.0073–0.4 | ? | ? | ? | Xenoestrogen |
p,p'-DDT | – | 0.03 | ? | ? | ? | Xenoestrogen |
Methoxychlor | p,p'-Dimethoxy-DDT | 0.01 (<0.001–0.02) | 0.01–0.13 | ? | ? | Xenoestrogen |
HPTE | Hydroxychlor; p,p'-OH-DDT | 1.2–1.7 | ? | ? | ? | Xenoestrogen |
Testosterone | T; 4-Androstenolone | <0.0001–<0.01 | <0.002–0.040 | >5000 | >5000 | Androgen |
Dihydrotestosterone | DHT; 5α-Androstanolone | 0.01 (<0.001–0.05) | 0.0059–0.17 | 221–>5000 | 73–1688 | Androgen |
Nandrolone | 19-Nortestosterone; 19-NT | 0.01 | 0.23 | 765 | 53 | Androgen |
Dehydroepiandrosterone | DHEA; Prasterone | 0.038 (<0.001–0.04) | 0.019–0.07 | 245–1053 | 163–515 | Androgen |
5-Androstenediol | A5; Androstenediol | 6 | 17 | 3.6 | 0.9 | Androgen |
4-Androstenediol | – | 0.5 | 0.6 | 23 | 19 | Androgen |
4-Androstenedione | A4; Androstenedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
3α-Androstanediol | 3α-Adiol | 0.07 | 0.3 | 260 | 48 | Androgen |
3β-Androstanediol | 3β-Adiol | 3 | 7 | 6 | 2 | Androgen |
Androstanedione | 5α-Androstanedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
Etiocholanedione | 5β-Androstanedione | <0.01 | <0.01 | >10000 | >10000 | Androgen |
Methyltestosterone | 17α-Methyltestosterone | <0.0001 | ? | ? | ? | Androgen |
Ethinyl-3α-androstanediol | 17α-Ethynyl-3α-adiol | 4.0 | <0.07 | ? | ? | Estrogen |
Ethinyl-3β-androstanediol | 17α-Ethynyl-3β-adiol | 50 | 5.6 | ? | ? | Estrogen |
Progesterone | P4; 4-Pregnenedione | <0.001–0.6 | <0.001–0.010 | ? | ? | Progestogen |
Norethisterone | NET; 17α-Ethynyl-19-NT | 0.085 (0.0015–<0.1) | 0.1 (0.01–0.3) | 152 | 1084 | Progestogen |
Norethynodrel | 5(10)-Norethisterone | 0.5 (0.3–0.7) | <0.1–0.22 | 14 | 53 | Progestogen |
Tibolone | 7α-Methylnorethynodrel | 0.5 (0.45–2.0) | 0.2–0.076 | ? | ? | Progestogen |
Δ4-Tibolone | 7α-Methylnorethisterone | 0.069–<0.1 | 0.027–<0.1 | ? | ? | Progestogen |
3α-Hydroxytibolone | – | 2.5 (1.06–5.0) | 0.6–0.8 | ? | ? | Progestogen |
3β-Hydroxytibolone | – | 1.6 (0.75–1.9) | 0.070–0.1 | ? | ? | Progestogen |
Footnotes: a = (1) Binding affinity values are of the format "median (range)" (# (#–#)), "range" (#–#), or "value" (#) depending on the values available. The full sets of values within the ranges can be found in the Wiki code. (2) Binding affinities were determined via displacement studies in a variety of in-vitro systems with labeled estradiol and human ERα and ERβ proteins (except the ERβ values from Kuiper et al. (1997), which are rat ERβ). Sources: See template page. |
References
[edit]- ^ a b Elva G. Shipley (1962). "Anti-gonadotropic steroids, inhibition of ovulation and mating". In Dorfman RI (ed.). Bioassay. Elsevier. pp. 179–274. ISBN 978-1-4832-7276-4.
- ^ Boccabella A, Bakritges C (January 1956). "Effects of ethandrostate on pituitary and sex organs of rats". Anatomical Record. 124 (2): 260.
- ^ a b c d Clinton R, Neumann H, Laskowski S, Christiansen R (1957). "Notes - Esters of 17α-Ethinyl-androstane-3β,17β-diol and 17 α-Ethinylandrost-5-ene-3β, 17β-diol". The Journal of Organic Chemistry. 22 (4): 473–475. doi:10.1021/jo01355a627. ISSN 0022-3263.
- ^ a b c d Olson KB, Frawley TF, Stein AA, Shields D (1958). "Ethandrostate: endocrine effects and studies in treatment of cancer". Cancer. 11 (3): 537–45. doi:10.1002/1097-0142(195805/06)11:3<537::aid-cncr2820110313>3.0.co;2-w. PMID 13523561. S2CID 738607.