4-methoxyestradiol

4-methoxyestradiol is an endogenous metabolite of estradiol, produced through the methylation of 4-hydroxyestradiol by the enzyme catechol-O-methyltransferase (COMT). It is a member of the methoxyestrogen family and is distinguished by its potent anti-proliferative and pro-apoptotic activities in various cancer cell lines, particularly renal cell carcinoma (RCC). The compound's mechanism of action involves the up-regulation of growth arrest- and DNA damage-inducible protein alpha (GADD45α), which subsequently triggers cell cycle arrest and apoptosis. Unlike its precursor 4-hydroxyestradiol, which can be oxidized to reactive quinones that damage DNA, 4-methoxyestradiol is considered a protective, non-genotoxic metabolite that may help prevent estrogen-driven carcinogenesis.

Other names

4-methoxy-17beta-estradiol4-MeO-E2