Molecular targeting of protein kinases to optimize selectivity and resistance profiles of kinase inhibitors.
This article reviews several important observations in the field of protein kinase drug discovery, exemplified mainly by targeting c-Abl for the treatment of CML. Structure-based strategy and insight are provided for the optimization of the selectivity and resistant mutation profiles of protein kinase inhibitors.
Liao
Jeffrey Jie-Lou
JJ
TransTech Pharma Inc., 4170 Mendenhall Oaks Pkwy, High Point, NC 27265, USA. jliao@ttpharma.com
D001665:Binding Sites; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D011494:Protein Kinases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D011494:Protein Kinases