Chemistry:Epitiostanol
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| Trade names | Thiodrol |
| Other names | Epithiostanol; Epithioandrostanol; 10275-S; 2α,3α-Epithio-5α-androstan-17β-ol; 2α,3α-Epithio-4,5α-dihydrotestosterone; 2α,3α-Epithio-DHT |
| Routes of administration | Intramuscular injection |
| Drug class | Androgen; Anabolic steroid; Antiestrogen |
| Identifiers | |
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| Chemical and physical data | |
| Formula | C19H30OS |
| Molar mass | 306.51 g·mol−1 |
| 3D model (JSmol) | |
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Epitiostanol, sold under the brand name Thiodrol, is an injected antiestrogen and anabolic–androgenic steroid (AAS) of the dihydrotestosterone (DHT) group which was described in the literature in 1965 and has been marketed in Japan as an antineoplastic agent for the treatment of breast cancer since 1977.[1][2][3][4][5]
Medical uses
Epitiostanol is used as an antiestrogen and antineoplastic agent in the treatment of breast cancer.[1][2][3][4][5] It has also been found to be effective in the treatment of gynecomastia.[6][7]
Side effects
A prodrug of epitiostanol, mepitiostane, which is also marketed for the treatment of breast cancer, is reported to show a high rate of virilizing side effects such as acne, hirsutism, and voice changes in women.[8]
Pharmacology
Pharmacodynamics
Epitiostanol binds directly to the androgen receptor (AR) and estrogen receptor (ER), where it acts as an agonist and antagonist, respectively.[3][5][9][10] It is described as potent in its activity as an antiestrogen and comparatively weak as an AAS.[7] In any case, in terms of AAS potency, epitiostanol has been found to have 11 times the anabolic activity and approximately equal androgenic activity relative to that of the reference AAS methyltestosterone.[11] The mechanism of action of epitiostanol in breast cancer is multimodal; it directly suppresses tumor growth through activation of the AR and inhibition of the ER, and, in premenopausal women, it additionally acts as an antigonadotropin and reducing systemic estrogen levels via AR activation and consequent suppression of the hypothalamic-pituitary-gonadal axis.[5][12] Epitiostanol is unique among AAS in acting as an antagonist of the ER.[citation needed]
Pharmacokinetics
Similarly to the case of testosterone, epitiostanol shows poor bioavailability and weak therapeutic efficacy when taken orally due to extensive first-pass metabolism.[13] As such, it must instead be administered via intramuscular injection.[13]
Chemistry
Epitiostanol, also known as 2α,3α-epithio-4,5α-dihydrotestosterone (2α,3α-epithio-DHT) or as 2α,3α-epithio-5α-androstan-17β-ol, is a synthetic androstane steroid and a derivative of DHT.[1][2] Mepitiostane, a derivative of epitiostanol with a C17α methoxycyclopentane ether substitution, is an orally active prodrug of epitiostanol.[14][15] Another derivative, methylepitiostanol (2α,3α-epithio-17α-methyl-5α-androstan-17β-ol), has a methyl group at the C17α position and is similarly an orally active variant of epitiostanol; it has surfaced as a novel designer steroid.[12]
Society and culture
Generic names
Epitiostanol is the generic name of the drug and its INN and JAN.[1][2]
References
- ↑ 1.0 1.1 1.2 1.3 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 492–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA492.
- ↑ 2.0 2.1 2.2 2.3 Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 394–. ISBN 978-3-88763-075-1. https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA394.
- ↑ 3.0 3.1 3.2 QSAR and Drug Design: New Developments and Applications. Elsevier. 20 November 1995. pp. 125, 145. ISBN 978-0-08-054500-4. https://books.google.com/books?id=I-Y4u2OQ5M0C&pg=PA145.
- ↑ 4.0 4.1 William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1455–. ISBN 978-0-8155-1856-3. https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1455.
- ↑ 5.0 5.1 5.2 5.3 "Antitumor effect of two oral steroids, mepitiostane and fluoxymesterone, on a pregnancy-dependent mouse mammary tumor (TPDMT-4)". Cancer Research 37 (12): 4408–4415. December 1977. PMID 922732.
- ↑ "Effects of 2alpha, 3alpha-epithio-5alpha-androstan-17beta-ol (epitiostanol) on hypothalamo-pituitary-gonadal axis in humans". Acta Obstetrica et Gynaecologica Japonica (Japanese Obstetrical and Gynecological Society) 22 (1): 42–8. January 1975. PMID 1224948.
- ↑ 7.0 7.1 "2α 3α-Epithio-5α-androstan-17β-ol in Treatment of Gynecomastia". Japanese Journal of Clinical Oncology 3 (2): 99–104. December 1973. doi:10.1093/oxfordjournals.jjco.a039832. ISSN 1465-3621.
- ↑ "Therapeutic value of mepitiostane in the treatment of advanced breast cancer". Cancer Treatment Reports 62 (5): 743–745. May 1978. PMID 657160.
- ↑ "Hormone Dependence and Independence in Mammary Tumors in Mice". International Review of Cytology. 103. Academic Press. 27 June 1986. pp. 319–. ISBN 978-0-08-058640-3. https://books.google.com/books?id=8SuUZFjkGpwC&pg=PA319.
- ↑ "Possible roles of sex steroids in the control of reproduction in bivalve molluscs". Aquaculture 272 (1–4): 76–86. 2007. doi:10.1016/j.aquaculture.2007.06.031. ISSN 0044-8486.
- ↑ "Sex Hormones (Male): Analogs and Antagonists". Encyclopedia of Molecular Cell Biology and Molecular Medicine. Wiley-VCH Verlag GmbH & Co. KGaA. 2006. doi:10.1002/3527600906.mcb.200500066. ISBN 3527600906.
- ↑ 12.0 12.1 "Designer steroids - over-the-counter supplements and their androgenic component: review of an increasing problem". Andrology 3 (2): 150–155. March 2015. doi:10.1111/andr.307. PMID 25684733.
- ↑ 13.0 13.1 "Absorption and disposition of epithiosteroids in rats (2): Avoidance of first-pass metabolism of mepitiostane by lymphatic absorption". Xenobiotica; the Fate of Foreign Compounds in Biological Systems 21 (7): 873–880. July 1991. doi:10.3109/00498259109039527. PMID 1776263.
- ↑ "Intrinsic lymphatic partition rate of mepitiostane, epitiostanol, and oleic acid absorbed from rat intestine". Pharmaceutical Research 8 (10): 1302–1306. October 1991. doi:10.1023/A:1015864131681. PMID 1796049.
- ↑ "Factors determining the intrinsic lymphatic partition rate of epitiostanol and mepitiostane". Pharmaceutical Research 9 (12): 1617–1621. December 1992. doi:10.1023/A:1015824710957. PMID 1488406.
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- List of androgens/anabolic steroids
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