Research progress of dual-targeting CDKs regulators for cancer therapy

Cyclin-dependent kinases (CDKs) are a class of enzymes that catalyze protein phosphorylation during cell cycle progression and transcriptional regulation. CDKs are involved in cell cycle regulation in combination with cyclins, and have become promising anticancer drug targets. In recent years, the research of CDK inhibitors has made great progress. The latest generation of CDK inhibitors have shown high selectivity for specific CDK proteins, and significantly improved safety compared to pan-CDK inhibitors. However, because the development of cancer is usually accompanied by complex network mechanisms, selective single-target drugs have disadvantages such as resistance and limited efficacy. With the development of polypharmacology, CDK regulators with dual targeting ability provide an effective strategy to solve this problem, which have sparked extensive exploration by researchers worldwide. This article reviews the different designs of CDK dual-target regulators and their potential applications in cancer therapy.