2-Methoxyestradiol--a Unique Blend of Activities Generating a New Class of anti-tumour/anti-inflammatory Agents

Drug Discov Today. 2007 Jul;12(13-14):577-84. doi: 10.1016/j.drudis.2007.05.005. Epub 2007 Jun 26.


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.

Publication types

  • Review

MeSH terms

  • 2-Methoxyestradiol
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Anti-Inflammatory Agents* / adverse effects
  • Anti-Inflammatory Agents* / pharmacology
  • Anti-Inflammatory Agents* / therapeutic use
  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Drug Design
  • Estradiol / adverse effects
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • Estradiol / therapeutic use
  • Humans
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Quantitative Structure-Activity Relationship


  • Angiogenesis Inhibitors
  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Estradiol
  • 2-Methoxyestradiol