title: 2-Methoxyestradiol--a unique blend of activities generating a new class of anti-tumour/anti-inflammatory agents.
abstract: The estradiol metabolite, 2-methoxyestradiol (2MEO), is currently being evaluated in Phase II clinical trials for the treatment of solid tumours and is undergoing preclinical evaluation for inflammatory conditions. The anti-proliferative/cytotoxic/pro-apoptotic effects on tumour and endothelial cells have conferred potential on this metabolite for a synergistic impact on tumour growth. Exploitation of this synergy of 2MEO has previously required the combination of well-established cytotoxic agents with newer anti-angiogenic agents. This article reviews the pharmacology of 2MEO and describes the limitations inherent in its residual estrogen receptor affinity. The extent to which the metabolite 2MEO embodies an optimised therapeutic candidate is discussed. The challenges involved in using rational (3D QSAR-based) drug design to optimise the activity profile of analogues of 2MEO to provide additional members of this new class of anti-tumour/anti-inflammatory drug are also outlined.
authors.affiliation: Department of Pharmacology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Tara E
authors.initials: TE
authors.lastname: Sutherland
authors.forename: Robin L
authors.initials: RL
authors.lastname: Anderson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hughes
authors.forename: Emile
authors.initials: E
authors.lastname: Altmann
authors.forename: Michael
authors.initials: M
authors.lastname: Schuliga
authors.forename: James
authors.initials: J
authors.lastname: Ziogas
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Stewart
mesh_terms: D000077584:2-Methoxyestradiol; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D004958:Estradiol; D000077584:2-Methoxyestradiol