A comprehensive description of cyclin-dependent kinase 8 (CDK8) inhibitors as anticancer agents.

Cyclin-dependent Kinase 8 (CDK8) plays a pivotal role in transcriptional regulation by associating with mediator complexes or phosphorylating transcription factors. Recent studies have demonstrated that CDK8 is a promising therapeutic target for various malignancies, including colorectal, breast, melanoma, and prostate cancers. In the context of radiotherapy, CDK8 contributes to tumor cell survival under stress conditions, thereby facilitating invasion, metastasis, and drug resistance. Moreover, the diverse functions of CDK8 and its specific roles in multiple cancer types have garnered significant scientific interest. Consequently, the development of selective CDK8 inhibitors may offer novel therapeutic strategies for cancer treatment. This review systematically summarizes different classes of selective CDK8 inhibitors, analyzes their structural characteristics, and evaluates their structure-activity relationships (SARs). It aims to provide guidance for the design and development of more potent, selective, and drug-like CDK8 inhibitors.