Introduction: The dysregulation of CDK9 protein is greatly related to the proliferation and differentiation of various cancers due to its key role in the regulation of RNA transcription. Moreover, CDK9 inhibition can markedly downregulate the anti-apoptotic protein Mcl-1 which is essential for the survival of tumors. Thus, targeting CDK9 is considered to be a promising strategy for antitumor drug development, and the development of selective CDK9 inhibitors has gained increasing attention.
Areas covered: This review focuses on the development of selective CDK9 inhibitors reported in patent publications during the period 2020-2022, which were searched from SciFinder and Cortellis Drug Discovery Intelligence.
Expert opinion: Given that pan-CDK9 inhibitors may lead to serious side effects due to poor selectivity, the investigation of selective CDK9 inhibitors has attracted widespread attention. CDK9 inhibitors make some advance in treating solid tumors and possess the therapeutic potential in EGFR-mutant lung cancer. CDK9 inhibitors with short half-life and intravenous administration might result in transient target engagement and contribute to a better safety profile in vivo. However, more efforts are urgently needed to accelerate the development of CDK9 inhibitors, including the research on new binding modes between ligand and receptor or new protein binding sites.
Keywords: CDK9; Cancer; Mcl-1; inhibitors; transient inhibition.