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Shown to be an antianhydrogen. The active metabolite of the widely used non-steroidal antagonist flutamide

The active metabolite of the widely used non-steroidal antagonist Flutamide (F598850). Shown to be an antianhydrogen.

The active metabolite of the widely used non-steroidal antagonist Flutamide. Shown to be an antianhydrogen.

2-hydroxy Flutamide is the major metabolite formed during the metabolism of the non-steroidal antiandrogen flutamide by cytochrome P450 (CYP) isoforms CYP1A2 and CYP3A4. Through competitive inhibition of the binding of testosterone to the nuclear androgen receptor (AR; IC₅₀ = ~300-900), 2-hydroxy flutamide blocks the expression of AR target genes and prevents androgen-dependent stabilization of the AR. Compared to flutamide, 2-hydroxy flutamide is a more potent antiandrogen in vivo, demonstrating a higher binding affinity for the AR (0.1% binding affinity relative to dihydrotestosterone) and, thus, is the predominant contributor to the therapeutic effects of flutamide in the treatment of prostate cancer.

Hydroxyflutamide plays a role in preventing the binding of 5α-dihydrotestosterone (DHT) and testosterone to the androgen receptors.

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[2] heinlein c a, chang c. androgen receptor in prostate cancer[j]. endocrine reviews, 2004, 25(2): 276-308.
[3] shet m s, mcphaul m, fisher c w, et al. metabolism of the antiandrogenic drug (flutamide) by human cyp1a2[j]. drug metabolism and disposition, 1997, 25(11): 1298-1303.
[4] gao w, kim j, dalton j t. pharmacokinetics and pharmacodynamics of nonsteroidal androgen receptor ligands[j]. pharmaceutical research, 2006, 23(8): 1641-1658.