Structure tuning of pyrazolylpyrrole derivatives as ERK inhibitors utilizing dual tools; 3D-QSAR and side-chain hopping

Abstract

The ERK pathway is a well-known therapeutic target of cancer treatment with great advantage of selectivity between normal cells and cancer cells, and the number of direct ERK kinase inhibitors is quite limited considering large number of available ERK structure from PDB. Therefore, we tried to combine 3D-QSAR with side-chain hopping in an attempt to produce novel structures as ERK inhibitors. The predictive models with q 2 value of 0.867, r 2 value of 0.991 in CoMFA and q 2 value of 0.628, r 2 value of 0.950 in CoMSIA were used to select effective compounds from new library generated from side-chain hopping by CombiGlide. © 2011 Elsevier Ltd. All rights reserved.