Methods of using chemical libraries to search for new kinase inhibitors

摘要: The generation of selective inhibitors for specific protein kinases would provide new tools analyzing signal transduction pathways and possibly therapeutic agents. We have invented an approach to the development kinase based on unexpected binding mode 2,6,9-trisubstituted purines ATP site human CDK2. most potent inhibitor, purvalanol B (IC 50 =6 nM), binds with a 30-fold greater affinity than known CDK2 flavopiridol. cellular effects this class compounds were examined compared those flavopiridol by monitoring changes in mRNA expression levels all genes treated cells Saccharomyces cerevisiae using high-density oligonucleotide probe arrays.