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@article{Zhao:2016:10.2174/1568026616666160719165633,
author = {Zhao, W and Jamshidiha, M and Lanyon-Hogg, T and Recchi, C and Cota, E and Tate, EW},
doi = {10.2174/1568026616666160719165633},
journal = {Current Topics in Medicinal Chemistry},
pages = {16--29},
title = {Direct targeting of the Ras GTPase superfamily through structure-based design},
url = {http://dx.doi.org/10.2174/1568026616666160719165633},
volume = {16},
year = {2016}
}
TY - JOUR
AB - The Ras superfamily of small monomeric GTPases includes some of the most prominent cancer targets for which no selective therapeutic agent has yet been successfully developed. The turn of the millennium saw a resurgence of efforts to target these enzymes using new and improved biophysical techniques to overcome the perceived difficulties of insurmountably high affinity for guanosine nucleotides and flat, flexible topology lacking suitable pockets for small molecule inhibitors. Further, recent investigations have begun to probe the dynamic conformational status of GTP-bound Ras, opening up new mechanisms of inhibition. While much of the literature has focused on the oncogenic Ras proteins, particularly K-Ras, these represent only a small minority of therapeutically interesting targets within the superfamily; for example, the Rab GTPases are the largest subfamily of about 70 members, and present an as yet untapped class of potential targets. The present review documents the key methodologies employed to date in structure-guided attempts to drug the Ras GTPases, and forecasts their transferability to other similarly challenging proteins in the superfamily.
AU - Zhao,W
AU - Jamshidiha,M
AU - Lanyon-Hogg,T
AU - Recchi,C
AU - Cota,E
AU - Tate,EW
DO - 10.2174/1568026616666160719165633
EP - 29
PY - 2016///
SN - 1873-4294
SP - 16
TI - Direct targeting of the Ras GTPase superfamily through structure-based design
T2 - Current Topics in Medicinal Chemistry
UR - http://dx.doi.org/10.2174/1568026616666160719165633
UR - http://hdl.handle.net/10044/1/39223
VL - 16
ER -
Prof. Ed Tate
GSK Chair in Chemical Biology
Department of Chemistry
Molecular Sciences Research Hub, White City Campus,
82 Wood Lane, London, W12 0BZ
e.tate@imperial.ac.uk
Tel: +44 (0)20 759 + ext 43752 or 45821