From Structure Modification to Drug Launch: A Systematic Reviewof the Ongoing Development of Cyclin-Dependent Kinase Inhibitorsfor Multiple Cancer Therapy

Herein, we discuss more than 50 cyclin-dependentkinase (CDK) inhibitors that have been approved or haveundergone clinical trials and their therapeutic application inmultiple cancers. This review discusses the design strategies,structure-activity relationships, and efficacy performances of theseselective or nonselective CDK inhibitors. The theoretical basis ofearly broad-spectrum CDK inhibitors is similar to the scope ofchemotherapy, but because their toxicity is greater than the benefit,there is no clinical therapeutic window. The notion that selectiveCDK inhibitors have a safer therapeutic potential than pan-CDKinhibitors has been widely recognized during the research process.Four CDK4/6 inhibitors have been approved for the treatment ofbreast cancer or for prophylactic administration during chemotherapy to protect bone marrow and immune system function.Furthermore, the emerging strategies in thefield of CDK inhibitors are summarized briefly, and CDKs continue to be widelypursued as emerging anticancer drug targets for drug discovery

Automated summary

This article discusses the application of more than 50 approved or clinically trialed cyclin-dependent kinase (CDK) inhibitors in multiple cancers. It covers the design strategies, structure-activity relationships, and efficacy performances of both selective and non-selective CDK inhibitors. The review highlights the safer therapeutic potential of selective CDK inhibitors and the approval of four CDK4/6 inhibitors for breast cancer treatment. The emerging strategies in the field of CDK inhibitors are also briefly summarized.