Zanoterone

Zanoterone (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name) (former developmental code name WIN-49596), also known as (5α,17α)-1'-(methylsulfonyl)-1'-H-pregn-20-yno[3,2-c]pyrazol-17-ol,^[1] is a steroidal antiandrogen which was never marketed.^[2][3][4] It was investigated for the treatment of benign prostatic hyperplasia (BPH) but failed to demonstrate sufficient efficacy in phase II clinical trials, and also showed an unacceptable incidence rate and severity of side effects (e.g., breast pain and gynecomastia).^[4][5] As such, it was not further developed.^[4][5]

Zanoterone

Clinical data
Other names	WIN-49596; (5α,17α)-1'-(methylsulfonyl)-1'-H-pregn-20-yno[3,2-c]pyrazol-17-ol
Routes of administration	By mouth
Drug class	Steroidal antiandrogen
Identifiers
IUPAC name (1R,3aS,3bR,5aS,10aS,10bS,12aS)-1-ethynyl-10a,12a-dimethyl-8-(methylsulfonyl)-1,2,3,3a,3b,4,5,5a,6,8,10,10a,10b,11,12,12a-hexadecahydrocyclopenta[5,6]naphtho[1,2-f]indazol-1-ol
CAS Number	107000-34-0
PubChem CID	9844827
DrugBank	D06357
ChemSpider	8020541
UNII	XQ5V1W49JG
KEGG	D06357
ChEMBL	ChEMBL2079581
CompTox Dashboard (EPA)	DTXSID50147873
Chemical and physical data
Formula	C23H32N2O3S
Molar mass	416.58 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CC[C@@H]4[C@@]3(CC5=CN(N=C5C4)S(=O)(=O)C)C
InChI InChI=1S/C23H32N2O3S/c1-5-23(26)11-9-19-17-7-6-16-12-20-15(14-25(24-20)29(4,27)28)13-21(16,2)18(17)8-10-22(19,23)3/h1,14,16-19,26H,6-13H2,2-4H3/t16-,17+,18-,19-,21-,22-,23-/m0/s1 Key:MHDDZDPNIDVLNK-ZGIWMXSJSA-N

Zanoterone was derived from 5α-dihydroethisterone (5α-dihydro-17α-ethynyltestosterone).^[6][7] It is an antagonist of the androgen receptor (K_i = 2.2 μM; RBATooltip relative binding affinity compared to metribolone = 2.2%), and with the exception of antiprogestogenic activity in rat and rabbit models, is devoid of other hormonal activities.^[6][8] Zanoterone does not inhibit 5α-reductase, aromatase, or 3α- or 3β-hydroxysteroid dehydrogenase in vitro.^[6] The drug significantly increases testosterone and estradiol levels in men.^[9] Zanoterone has been found to not significantly inhibit mating performance or fertility in adult male rats at high dosages for an extended period of time.^[6] It has been found to act as an inducer of the enzyme CYP3A4 in vivo in rats.^[10]

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Relative potencies of selected antiandrogens

Antiandrogen	Relative potency
Bicalutamide	4.3
Hydroxyflutamide	3.5
Flutamide	3.3
Cyproterone acetate	1.0
Zanoterone	0.4
Description: Relative potencies of orally administered antiandrogens in antagonizing 0.8 to 1.0 mg/kg s.c.Tooltip subcutaneous injection testosterone propionate-induced ventral prostate weight increase in castrated immature male rats. Higher values mean greater potency. Sources: See template.

See also

• List of steroidal antiandrogens