Structural Basis for Targeting the Folded P-Loop Conformation of c-MET
Gavin W. Collie, Iacovos N. Michaelides, Kevin J. Embrey, Christopher J. Stubbs, Ulf Börjesson, Ian L. Dale, Arjan Snijder, Louise Barlind, Kun Song, Puneet Khurana, Christopher Phillips, Richard Storer
Abstract
) with nanomolar biochemical activity against c-MET and promising cell activity and kinase selectivity. These findings increase our structural understanding of the folded P-loop conformation of c-MET and provide a sound structural and chemical basis for further investigation of this underexplored yet potentially therapeutically exploitable conformational state.
Topics & Concepts
Loop (graph theory)ChemistryKinaseStereochemistryComputational biologyBiochemistryBiologyCombinatoricsMathematicsPI3K/AKT/mTOR signaling in cancerEnzyme function and inhibitionMelanoma and MAPK Pathways