Ontology highlight
ABSTRACT:
SUBMITTER: Koehler MF
PROVIDER: S-EPMC4789660 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
ACS medicinal chemistry letters 20160106 3
Beginning with promiscuous COT inhibitors, which were found to inhibit CDK8, a series of 6-aza-benzothiophene containing compounds were developed into potent, selective CDK8 inhibitors. When cocrystallized with CDK8 and cyclin C, these compounds exhibit an unusual binding mode, making a single hydrogen bond to the hinge residue A100, a second to K252, and a key cation-π interaction with R356. Structure-based drug design resulted in tool compounds 13 and 32, which are highly potent, kinase select ...[more]