Chemical compound
Pharmaceutical compound
Epitiostanol Clinical data 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 Intramuscular injection Drug class Androgen ;Anabolic steroid ;Antiestrogen Identifiers (1S ,3AS ,3bR ,5aS ,6aS ,7aR ,8aS ,8bS ,10aS )-8a,10a-dimethylhexadecahydro-1H -cyclopenta[7,8]phenanthro[2,3-b]thiiren-1-ol
CAS Number PubChem CID ChemSpider UNII CompTox Dashboard (EPA) Chemical and physical data Formula C 19 H 30 O S Molar mass −1 3D model (JSmol ) InChI=InChI=1S/C19H30OS/c1-18-8-7-14-12(13(18)5-6-17(18)20)4-3-11-9-15-16(21-15)10-19(11,14)2/h11-17,20H,3-10H2,1-2H3
Key:OBMLHUPNRURLOK-UHFFFAOYSA-N
Epitiostanol , sold under the brand nameThiodrol , is aninjected antiestrogen andanabolic–androgenic steroid (AAS) of thedihydrotestosterone (DHT) group which was described in the literature in 1965 and has been marketed inJapan as anantineoplastic agent for the treatment ofbreast cancer since 1977.[ 1] [ 2] [ 3] [ 4] [ 5]
Epitiostanol is used as an antiestrogen and antineoplastic agent in the treatment of breast cancer.[ 1] [ 2] [ 3] [ 4] [ 5] gynecomastia .[ 6] [ 7]
Aprodrug of epitiostanol,mepitiostane , which is also marketed for the treatment of breast cancer, is reported to show a high rate ofvirilizing side effects such asacne ,hirsutism , andvoice changes in women.[ 8]
Epitiostanol binds directly to theandrogen receptor (AR) andestrogen receptor (ER), where it acts as anagonist andantagonist , respectively.[ 3] [ 5] [ 9] [ 10] potent in its activity as an antiestrogen and comparatively weak as an AAS.[ 7] potency , epitiostanol has been found to have 11 times theanabolic activity and approximately equalandrogenic activity relative to that of the reference AASmethyltestosterone .[ 11] 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, inpremenopausal women, it additionally acts as anantigonadotropin and reducing systemicestrogen levels via AR activation and consequent suppression of thehypothalamic-pituitary-gonadal axis .[ 5] [ 12] [citation needed
Similarly to the case oftestosterone , epitiostanol shows poorbioavailability and weak therapeutic efficacy when takenorally due to extensivefirst-pass metabolism .[ 13] intramuscular injection .[ 13]
Epitiostanol, also known as 2α,3α-epithio-4,5α-dihydrotestosterone (2α,3α-epithio-DHT) or as 2α,3α-epithio-5α-androstan-17β-ol, is asynthetic androstane steroid and aderivative of DHT.[ 1] [ 2] Mepitiostane , a derivative of epitiostanol with a C17αmethoxycyclopentane ether substitution, is anorally active prodrug of epitiostanol.[ 14] [ 15] methylepitiostanol (2α,3α-epithio-17α-methyl-5α-androstan-17β-ol), has amethyl group at the C17α position and is similarly an orally active variant of epitiostanol; it has surfaced as a noveldesigner steroid .[ 12]
Society and culture [ edit ] Epitiostanol is thegeneric name of the drug and itsINN Tooltip International Nonproprietary Name andJAN Tooltip Japanese Accepted Name .[ 1] [ 2]
^a b c d Elks J (14 November 2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies ISBN 978-1-4757-2085-3 ^a b c d Index Nominum 2000: International Drug Directory ISBN 978-3-88763-075-1 ^a b c Timmerman H (20 November 1995).QSAR and Drug Design: New Developments and Applications ISBN 978-0-08-054500-4 ^a b William Andrew Publishing (22 October 2013).Pharmaceutical Manufacturing Encyclopedia, 3rd Edition ISBN 978-0-8155-1856-3 ^a b c d 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 . ^ Kurachi K, Aono T, Tomoyama J, Matsumoto K, Nakasima A (January 1975). "Effects of 2alpha, 3alpha-epithio-5alpha-androstan-17beta-ol (epitiostanol) on hypothalamo-pituitary-gonadal axis in humans".Acta Obstetrica et Gynaecologica Japonica .22 (1). Japanese Obstetrical and Gynecological Society:42– 8.PMID 1224948 . ^a b Abe O, Kumaoka S, Yamamoto H (December 1973). "2α 3α-Epithio-5α-androstan-17β-ol in Treatment of Gynecomastia".Japanese Journal of Clinical Oncology .3 (2):99– 104.doi :10.1093/oxfordjournals.jjco.a039832 .ISSN 1465-3621 . ^ 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 . ^ Matsuzawa A (27 June 1986)."Hormone Dependence and Independence in Mammary Tumors in Mice" . In Bourne GH, Heon KW, Friedlander M (eds.).International Review of Cytology . Vol. 103. Academic Press. pp. 319–.ISBN 978-0-08-058640-3 ^ Croll RP, Wang C (2007). "Possible roles of sex steroids in the control of reproduction in bivalve molluscs".Aquaculture .272 (1– 4):76– 86.Bibcode :2007Aquac.272...76C .doi :10.1016/j.aquaculture.2007.06.031 .ISSN 0044-8486 . ^ Brueggemeier RW (2006). "Sex Hormones (Male): Analogs and Antagonists".Encyclopedia of Molecular Cell Biology and Molecular Medicine . Wiley-VCH Verlag GmbH & Co. KGaA.doi :10.1002/3527600906.mcb.200500066 .ISBN 3-527-60090-6 ^a b 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 . ^a b Ichihashi T, Kinoshita H, Yamada H (July 1991). "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.doi :10.3109/00498259109039527 .PMID 1776263 . ^ Ichihashi T, Kinoshita H, Takagishi Y, Yamada H (October 1991). "Intrinsic lymphatic partition rate of mepitiostane, epitiostanol, and oleic acid absorbed from rat intestine".Pharmaceutical Research .8 (10):1302– 1306.doi :10.1023/A:1015864131681 .PMID 1796049 .S2CID 31203405 . ^ Ichihashi T, Takagishi Y, Yamada H (December 1992). "Factors determining the intrinsic lymphatic partition rate of epitiostanol and mepitiostane".Pharmaceutical Research .9 (12):1617– 1621.doi :10.1023/A:1015824710957 .PMID 1488406 .S2CID 2881279 .
Estrogens
ER Tooltip Estrogen receptor agonistsSteroidal: Alfatradiol Certainandrogens /anabolic steroids (e.g.,testosterone ,testosterone esters ,methyltestosterone ,metandienone ,nandrolone esters ) (via estrogenic metabolites) Certainprogestins (e.g.,norethisterone ,noretynodrel ,etynodiol diacetate ,tibolone ) Clomestrone Cloxestradiol acetate Conjugated estriol Conjugated estrogens Epiestriol Epimestrol Esterified estrogens Estetrol † Estradiol Estradiol esters (e.g.,estradiol acetate ,estradiol benzoate ,estradiol cypionate ,estradiol enanthate ,estradiol undecylate ,estradiol valerate ,polyestradiol phosphate ,estradiol ester mixtures (Climacteron ))Estramustine phosphate Estriol Estriol esters (e.g.,estriol succinate ,polyestriol phosphate )Estrogenic substances Estrone Estrone esters Ethinylestradiol # Hydroxyestrone diacetate Mestranol Methylestradiol Moxestrol Nilestriol Prasterone (dehydroepiandrosterone; DHEA) Promestriene Quinestradol Quinestrol Progonadotropins
Antiestrogens
ER Tooltip Estrogen receptor antagonistsSERMs Tooltip selective estrogen receptor modulators /SERDs Tooltip selective estrogen receptor downregulators )Aromatase inhibitors Antigonadotropins Androgens /anabolic steroids (e.g.,testosterone ,testosterone esters ,nandrolone esters ,oxandrolone ,fluoxymesterone )D2 receptor antagonists (prolactin releasers) (e.g.,domperidone ,metoclopramide ,risperidone ,haloperidol ,chlorpromazine ,sulpiride )GnRH agonists (e.g.,leuprorelin ,goserelin )GnRH antagonists (e.g.,cetrorelix ,elagolix )Progestogens (e.g.,chlormadinone acetate ,cyproterone acetate ,gestonorone caproate ,hydroxyprogesterone caproate ,medroxyprogesterone acetate ,megestrol acetate )Others
Androgens AAS Tooltip anabolic–androgenic steroid )
Antiandrogens
AR Tooltip Androgen receptor antagonists Steroidogenesis
Antigonadotropins D2 receptor antagonists (prolactin releasers ) (e.g.,domperidone ,metoclopramide ,risperidone ,haloperidol ,chlorpromazine ,sulpiride )Estrogens (e.g.,bifluranol ,diethylstilbestrol ,estradiol ,estradiol esters ,ethinylestradiol ,ethinylestradiol sulfonate ,paroxypropione )GnRH agonists (e.g.,leuprorelin )GnRH antagonists (e.g.,cetrorelix )Progestogens (incl.,chlormadinone acetate ,cyproterone acetate ,hydroxyprogesterone caproate ,gestonorone caproate ,medroxyprogesterone acetate ,megestrol acetate )Others
ER Tooltip Estrogen receptor
Agonists Steroidal: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol 3α-Androstanediol 3α,5α-Dihydrolevonorgestrel 3β,5α-Dihydrolevonorgestrel 3α-Hydroxytibolone 3β-Hydroxytibolone 3β-Androstanediol 4-Androstenediol 4-Androstenedione 4-Fluoroestradiol 4-Hydroxyestradiol 4-Hydroxyestrone 4-Methoxyestradiol 4-Methoxyestrone 5-Androstenediol 7-Oxo-DHEA 7α-Hydroxy-DHEA 7α-Methylestradiol 7β-Hydroxyepiandrosterone 8,9-Dehydroestradiol 8,9-Dehydroestrone 8β-VE2 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) 11β-Chloromethylestradiol 11β-Methoxyestradiol 15α-Hydroxyestradiol 16-Ketoestradiol 16-Ketoestrone 16α-Fluoroestradiol 16α-Hydroxy-DHEA 16α-Hydroxyestrone 16α-Iodoestradiol 16α-LE2 16β-Hydroxyestrone 16β,17α-Epiestriol (16β-hydroxy-17α-estradiol) 17α-Estradiol (alfatradiol )17α-Dihydroequilenin 17α-Dihydroequilin 17α-Epiestriol (16α-hydroxy-17α-estradiol) 17α-Ethynyl-3α-androstanediol 17α-Ethynyl-3β-androstanediol 17β-Dihydroequilenin 17β-Dihydroequilin 17β-Methyl-17α-dihydroequilenin Abiraterone Abiraterone acetate Alestramustine Almestrone Anabolic steroids (e.g.,testosterone andesters ,methyltestosterone ,metandienone (methandrostenolone) ,nandrolone andesters , many others; via estrogenic metabolites)Atrimustine Bolandiol Bolandiol dipropionate Butolame Clomestrone Cloxestradiol Conjugated estriol Conjugated estrogens Cyclodiol Cyclotriol DHEA DHEA-S ent -EstradiolEpiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol) Epimestrol Equilenin Equilin ERA-63 (ORG-37663) Esterified estrogens Estetrol Estradiol Estramustine Estramustine phosphate Estrapronicate Estrazinol Estriol Estrofurate Estrogenic substances Estromustine Estrone Etamestrol (eptamestrol) Ethinylandrostenediol Ethinylestradiol Ethinylestriol Ethylestradiol Etynodiol Etynodiol diacetate Hexolame Hippulin Hydroxyestrone diacetate Lynestrenol Lynestrenol phenylpropionate Mestranol Methylestradiol Moxestrol Mytatrienediol Nilestriol Norethisterone Noretynodrel Orestrate Pentolame Prodiame Prolame Promestriene RU-16117 Quinestradol Quinestrol Tibolone Xenoestrogens: Anise -related (e.g.,anethole ,anol ,dianethole ,dianol ,photoanethole )Chalconoids (e.g.,isoliquiritigenin ,phloretin ,phlorizin (phloridzin) ,wedelolactone )Coumestans (e.g.,coumestrol ,psoralidin )Flavonoids (incl.7,8-DHF ,8-prenylnaringenin ,apigenin ,baicalein ,baicalin ,biochanin A ,calycosin ,catechin ,daidzein ,daidzin ,ECG ,EGCG ,epicatechin ,equol ,formononetin ,glabrene ,glabridin ,genistein ,genistin ,glycitein ,kaempferol ,liquiritigenin ,mirificin ,myricetin ,naringenin ,penduletin ,pinocembrin ,prunetin ,puerarin ,quercetin ,tectoridin ,tectorigenin )Lavender oil Lignans (e.g.,enterodiol ,enterolactone ,nyasol (cis -hinokiresinol) )Metalloestrogens (e.g.,cadmium )Pesticides (e.g.,alternariol ,dieldrin ,endosulfan ,fenarimol ,HPTE ,methiocarb ,methoxychlor ,triclocarban ,triclosan )Phytosteroids (e.g.,digitoxin (digitalis ),diosgenin ,guggulsterone )Phytosterols (e.g.,β-sitosterol ,campesterol ,stigmasterol )Resorcylic acid lactones (e.g.,zearalanone ,α-zearalenol ,β-zearalenol ,zearalenone ,zeranol (α-zearalanol) ,taleranol (teranol, β-zearalanol) )Steroid -like (e.g.,deoxymiroestrol ,miroestrol )Stilbenoids (e.g.,resveratrol ,rhaponticin )Synthetic xenoestrogens (e.g.,alkylphenols ,bisphenols (e.g.,BPA ,BPF ,BPS ),DDT ,parabens ,PBBs ,PHBA ,phthalates ,PCBs )Others (e.g.,agnuside ,rotundifuran ) MixedSERMs Tooltip Selective estrogen receptor modulators ) Antagonists Coregulator-binding modulators: ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown
