TY - JOUR
T1 - 2-Methoxyestradiol - a unique blend of activities generating a new class of anti-tumour/anti-inflammatory agents
AU - Sutherland, Tara E.
AU - Anderson, Robin L.
AU - Hughes, Richard A.
AU - Altmann, Emile
AU - Schuliga, Michael
AU - Ziogas, James
AU - Stewart, Alastair G.
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34447106558&partnerID=8YFLogxK
U2 - 10.1016/j.drudis.2007.05.005
DO - 10.1016/j.drudis.2007.05.005
M3 - Review Article
C2 - 17631253
AN - SCOPUS:34447106558
SN - 1359-6446
VL - 12
SP - 577
EP - 584
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 13-14
ER -