title: Therapeutic promises of 2-methoxyestradiol and its drug disposition challenges.
abstract: 2-Methoxyestradiol (2MeO-E2) is an endogenous metabolite of estrogen which was initially considered to be inactive. During the last few decades it has been shown that 2MeO-E2 is a promising anticancer drug. In vitro experiments have demonstrated that it has several anticancer activities, and potential to alleviate hypertension, glomerulosclerosis, hypercholesterolemia, and other disorders. However, due to its low solubility and extensive glucuronidation, to achieve effective concentrations large doses of 2MeO-E2 would be required. Clinical studies reflected very high inter- and intrapatient variability and oral bioavailability of 1 to 2%. Thus, this review paper highlights the origin of this compound, its therapeutic promises, and possible mechanisms of action. It also discusses the pharmacokinetic properties of 2MeO-E2 as well as current developments to overcome low drug solubility and its extensive first pass metabolism.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, PO Box 980533, Richmond, Virginia 23298-0581, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Verenich
authors.forename: Phillip M
authors.initials: PM
authors.lastname: Gerk
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D004958:Estradiol; D000077584:2-Methoxyestradiol