Synthesis and biological evaluation of small molecule modulators of CDK8/Cyclin C complex with phenylaminoquinoline scaffold.

ABSTRACT:

Background

CDK8/CycC complex has kinase activity towards the carboxyterminal domain of RNA polymerase II, and contributes to the regulation of transcription via association with the mediator complex. Different human malignancies, mainly colorectal and gastric cancers, were produced as a result of overexpression of CDK8/CycC in the mediator complex. Therefore, CDK8/CycC complex represents as a cancer oncogene and it has become a potential target for developing CDK8/CycC modulators.

Methods

A series of nine 4-phenylaminoquinoline scaffold-based compounds 5a-i was synthesized, and biologically evaluated as potential CDK8/CycC complex inhibitors.

Results

The scaffold substituent effects on the intrinsic inhibitory activity toward CDK8/CycC complex are addressed try

SUBMITTER: Al-Sanea MM 

PROVIDER: S-EPMC7075364 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature