Heterocyclic Compounds as CDK9 Inhibitors: Structural Diversity, Mechanism of Action, and Therapeutic Potential in Cancer and Beyond

Cyclin-dependent kinases (CDKs) are crucial proteins involved in key cellular processes, such as cell division and transcription. Their dysregulation plays a significant role in cancer development. Inhibiting cyclin-dependent kinase 9 (CDK9) impacts several survival pathways in cancer cells, presenting a promising therapeutic approach for various cancers. CDK9, in association with cyclin T1, forms the positive transcription elongation factor b (P-TEFb) complex, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II (Pol II). This phosphorylation promotes the transition from transcription initiation to elongation. This review examines recent advancements in CDK9 modulators, with a particular emphasis on compounds currently in clinical trials.