Identification of a kinase profile that predicts chromosome damage induced by small molecule kinase inhibitors.

ABSTRACT: Kinases are heavily pursued pharmaceutical targets because of their mechanistic role in many diseases. Small molecule kinase inhibitors (SMKIs) are a compound class that includes marketed drugs and compounds in various stages of drug development. While effective, many SMKIs have been associated with toxicity including chromosomal damage. Screening for kinase-mediated toxicity as early as possible is crucial, as is a better understanding of how off-target kinase inhibition may give rise to chromosomal damage. To that end, we employed a competitive binding assay and an analytical method to predict the toxicity of SMKIs. Specifically, we developed a model based on the binding affinity of SMKIs to a panel of kinases to predict whether a compound tests positive for chromosome damage. As trainin

SUBMITTER: Olaharski AJ 

PROVIDER: S-EPMC2704959 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature