Binding patterns and structure-activity relationship of CDK8 inhibitors

A major goal of medicinal chemists is to identify and validate novel and effective kinase targets for treatment of cancer. Recent studies have shown that cyclin-dependent kinase 8 (CDK8) is a target for treatment of colorectal, breast, melanoma, and prostate cancers. The crystal structure of CDK8 has been reported, and eutectic interactions have been identified for 24 compounds that target CDK8. To more effectively develop CDK8 inhibitors, particularly those with improved selectivity, we summarized the structure, structure-activity relationships, and binding information of typical CDK8 inhibitors, which may serve as a reference for development of novel CDK8 inhibitors.