Mepitiostane

Mepitiostane, sold under the brand name Thioderon, is an orally active antiestrogen and anabolic–androgenic steroid (AAS) of the dihydrotestosterone (DHT) group which is marketed in Japan as an antineoplastic agent for the treatment of breast cancer.^{[1][2][3][4][5]} It is a prodrug of epitiostanol.^[6][7] The drug was patented and described in 1968.^[1]

Mepitiostane

Clinical data
Trade names	Thioderon
Other names	10364-S; Epitiostanol 17β-(1-methoxy)cyclopentyl ether; 17β-[(1-Methoxycyclopentyl)oxy]-2α,3α-epithio-5α-androstane
AHFS/Drugs.com	International Drug Names
Routes of administration	By mouth
Drug class	Androgen; Anabolic steroid; Androgen ether; Antiestrogen
ATC code	None
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name (1S,2S,4R,8S,11R,12S,15S,16S)-15-[(1-methoxycyclopentyl)oxy]-2,16-dimethyl-5-thiapentacyclo[9.7.0.02,8.04,6.012,16]octadecane
CAS Number	21362-69-6 Y
PubChem CID	9909202
ChemSpider	8084854 N
UNII	O00404969K
KEGG	D01602 Y
CompTox Dashboard (EPA)	DTXSID001016882
Chemical and physical data
Formula	C25H40O2S
Molar mass	404.65 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2OC4(CCCC4)OC)CC[C@@H]5[C@@]3(C[C@@H]6[C@H](C5)S6)C
InChI InChI=1S/C25H40O2S/c1-23-13-10-19-17(7-6-16-14-20-21(28-20)15-24(16,19)2)18(23)8-9-22(23)27-25(26-3)11-4-5-12-25/h16-22H,4-15H2,1-3H3/t16-,17-,18-,19-,20-,21+,22-,23-,24-/m0/s1 N Key:IVDYZAAPOLNZKG-KWHRADDSSA-N N
NY (what is this?)  (verify)

Medical uses

Mepitiostane is used as an antiestrogen and antineoplastic agent in the treatment of breast cancer.^[1][2][3][5] It is also used as an AAS in the treatment of anemia of renal failure.^[5] A series of case reports have found it to be effective in the treatment of an estrogen receptor (ER)-dependent meningiomas as well.^{[8][9][10][11]}

Side effects

See also: Anabolic steroid § Adverse effects

Mepitiostane shows a high rate of virilizing side effects such as acne, hirsutism, and voice changes in women.^[12]

Pharmacology

Pharmacodynamics

Mepitiostane is described as similar to tamoxifen as an antiestrogen,^[8] and through its active form epitiostanol, binds directly to and antagonizes the ER.^{[13][14][15][16]} It is also an AAS.^[1][3]

Pharmacokinetics

Mepitiostane is converted into epitiostanol in the body.^[6][7]

Chemistry

See also: List of androgens/anabolic steroids

Mepitiostane, also known as epitiostanol 17β-(1-methoxy)cyclopentyl ether,^[6] is a synthetic androstane steroid and a derivative of DHT.^[1][2][3] It is the C17β (1-methoxy)cyclopentyl ether of epitiostanol, which itself is 2α,3α-epithio-DHT or 2α,3α-epithio-5α-androstan-17β-ol.^[6][17] A related AAS is methylepitiostanol (17α-methylepitiostanol), which is an orally active variant of epitiostanol similarly to mepitiostane, though also has a risk of hepatotoxicity.^[18]

Society and culture

Generic names

Mepitiostane is the generic name of the drug and its INNTooltip International Nonproprietary Name and JANTooltip Japanese Accepted Name.^[1][2][3]

References

1. Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. p. 768. ISBN 978-1-4757-2085-3.
2. Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 648–. ISBN 978-3-88763-075-1.
3. Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 175–. ISBN 978-94-011-4439-1.
4. "Mepitiostane".
5. Erslev AJ (1991). Erythropoietin: molecular, cellular, and clinical biology. Johns Hopkins University Press. p. 229. ISBN 978-0-8018-4221-4.
6. Stella V, Borchardt R, Hageman M, Oliyai R, Maag H, Tilley J, eds. (12 March 2007). Prodrugs: Challenges and Rewards. Springer Science & Business Media. pp. 660–. ISBN 978-0-387-49782-2.
7. Borchardt RT, Smith PL, Wilson G (29 June 2013). Models for Assessing Drug Absorption and Metabolism. Springer Science & Business Media. pp. 101–. ISBN 978-1-4899-1863-5.
8. Newton HB (19 December 2005). Handbook of Brain Tumor Chemotherapy. Academic Press. pp. 470–. ISBN 978-0-08-045593-8.
9. Lee JH (11 December 2008). Meningiomas: Diagnosis, Treatment, and Outcome. Springer Science & Business Media. pp. 293–5. ISBN 978-1-84628-784-8.
10. Oura S, Sakurai T, Yoshimura G, Tamaki T, Umemura T, Kokawa Y, et al. (July 2000). "Regression of a presumed meningioma with the antiestrogen agent mepitiostane. Case report". Journal of Neurosurgery. 93 (1): 132–135. doi:10.3171/jns.2000.93.1.0132. PMID 10883917.
11. Miyai M, Takenaka K, Hayashi K, Kato M, Uematsu K, Murai H (August 2014). "[Effect of an oral anti-estrogen agent (mepitiostane) on the regression of intracranial meningiomas in the elderly]". Brain and Nerve = Shinkei Kenkyu No Shinpo (in Japanese). 66 (8): 995–1000. PMID 25082321.
12. Inoue K, Okazaki K, Morimoto T, Hayashi M, Uyama S, Sonoo H, et al. (May 1978). "Therapeutic value of mepitiostane in the treatment of advanced breast cancer". Cancer Treatment Reports. 62 (5): 743–745. PMID 657160.
13. Matsuzawa A, Yamamoto T (December 1977). "Antitumor effect of two oral steroids, mepitiostane and fluoxymesterone, on a pregnancy-dependent mouse mammary tumor (TPDMT-4)". Cancer Research. 37 (12): 4408–4415. PMID 922732.
14. Timmerman H (20 November 1995). QSAR and Drug Design: New Developments and Applications. Elsevier. pp. 125, 145. ISBN 978-0-08-054500-4.
15. Matsuzawa A (1986). "Hormone dependence and independence of mammary tumors in mice". International Review of Cytology. 103: 303–40. doi:10.1016/s0074-7696(08)60839-6. ISBN 9780123645036. PMID 3017886.
16. Croll RP, Wang C (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.
17. Porter CJ, Charman WN (29 June 2013). "Model Systems for Intestinal Lympahtic Transport Studies". In Borchardt RT, Smith PL, Wilson G (eds.). Models for Assessing Drug Absorption and Metabolism. Springer Science & Business Media. pp. 101–. ISBN 978-1-4899-1863-5.
18. Rahnema CD, Crosnoe LE, Kim ED (March 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. PMID 25684733. S2CID 6999218.