Epitiostanol

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Epitiostanol
Epitiostanol.png
Systematic (IUPAC) name
(2α,3α,5α,17β)-2,3-epithioandrostan-17-ol
Clinical data
Trade names Thiodrol
Routes of
administration
Injection
Identifiers
CAS Number 2363-58-8
PubChem CID 3243
ChemSpider 391989
Chemical data
Formula C19H30OS
Molar mass 306.5059 g/mol

Epitiostanol (INN, JAN) (brand name Thiodrol), also known as epithioandrostanol or 2α,3α-epithio-5α-androstan-17β-ol, is a sulfur-containing, steroidal, potent antiestrogen as well as androgen and anabolic steroid derived from androstanol (5α-androstan-3α-ol) that has been marketed in Japan as an antineoplastic agent for the treatment of breast cancer since 1977.[1][2][3][4][5] The drug has also been found to be effective in the treatment of gynecomastia.[6][1] Epitiostanol binds directly to the estrogen and androgen receptors, where it acts as an antagonist and an agonist, respectively.[3][5][7][8] The mechanism of action of epitiostanol in breast cancer is multimodal; it directly suppresses tumor growth through local tissue interactions with the estrogen and androgen receptors, and, in premenopausal women, it additionally acts as an antigonadotropin and reduces systemic estrogen levels through activation of the androgen receptor and consequent suppression of the hypothalamic-pituitary-gonadal axis.[5][9]

Similarly to the case of testosterone (which is closely related structurally), epitiostanol shows poor bioavailability and weak therapeutic activity when taken orally due to extensive first-pass metabolism and must instead be administered via injection.[10] Mepitiostane, a derivative of epitiostanol with a methoxycyclopentane ether substitution at the 17α position, is an oral prodrug of epitiostanol that has subsequently been developed.[11][12] Another derivative, methylepitiostanol (2α,3α-epithio-17α-methyl-5α-androstan-17β-ol), also referred to as "epistane", has a methyl group at the 17α position and is similarly an oral version of epitiostanol; it has surfaced as a novel designer steroid.[9] The compound may degrade to the controlled anabolic steroid desoxymethyltestosterone.[9]

Epitiostanol, mepitiostane, and methylepitiostanol are unique among anabolic steroids in acting as antiestrogens.

See also[edit]

References[edit]

  1. ^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 492–. ISBN 978-1-4757-2085-3. 
  2. ^ Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 394–. ISBN 978-3-88763-075-1. 
  3. ^ a b H. Timmerman (20 November 1995). QSAR and Drug Design: New Developments and Applications. Elsevier. pp. 125, 145. ISBN 978-0-08-054500-4. 
  4. ^ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1455–. ISBN 978-0-8155-1856-3. 
  5. ^ a b c Matsuzawa A, Yamamoto T (1977). "Antitumor effect of two oral steroids, mepitiostane and fluoxymesterone, on a pregnancy-dependent mouse mammary tumor (TPDMT-4)". Cancer Res. 37 (12): 4408–15. PMID 922732. 
  6. ^ Acta obstetrica et gynecologica japonica. Japanese Obstetrical and Gynecological Society. 1975. 
  7. ^ INTERNATIONAL REVIEW OF CYTOLOGY. Academic Press. 27 June 1986. pp. 319–. ISBN 978-0-08-058640-3. 
  8. ^ Croll, Roger P.; Wang, Chunde (2007). "Possible roles of sex steroids in the control of reproduction in bivalve molluscs". Aquaculture. 272 (1-4): 76–86. doi:10.1016/j.aquaculture.2007.06.031. ISSN 0044-8486. 
  9. ^ a b c Rahnema, C. D.; Crosnoe, L. E.; Kim, E. D. (2015). "Designer steroids - over-the-counter supplements and their androgenic component: review of an increasing problem". Andrology. 3 (2): 150–155. doi:10.1111/andr.307. ISSN 2047-2919. 
  10. ^ Ichihashi, T.; Kinoshita, H.; Yamada, H. (2009). "Absorption and disposition of epithiosteroids in rats (2): Avoidance of first-pass metabolism of mepitiostane by lymphatic absorption". Xenobiotica. 21 (7): 873–880. doi:10.3109/00498259109039527. ISSN 0049-8254. 
  11. ^ Ichihashi, Teruhisa; Kinoshita, Haruki; Takagishi, Yasushi; Yamada, Hideo (1991). Pharmaceutical Research. 08 (10): 1302–1306. doi:10.1023/A:1015864131681. ISSN 0724-8741.  Missing or empty |title= (help)
  12. ^ Ichihashi, Teruhisa; Takagishi, Yasushi; Yamada, Hideo (1992). Pharmaceutical Research. 09 (12): 1617–1621. doi:10.1023/A:1015824710957. ISSN 0724-8741.  Missing or empty |title= (help)