Cyclin-dependent kinase 1 (CDK1), Cyclin-dependent kinase 2 (CDK2), Cyclin-dependent kinase 4 (CDK4), Cyclin-dependent kinase 6 (CDK6), and Cyclin-dependent kinase 9 (CDK9) (CDK1/2/4/6/9)

Cyclin-dependent kinases (CDKs) 1, 2, 4, 6, and 9 are a group of serine/threonine kinases that serve as critical regulators of the eukaryotic cell cycle and gene transcription [1, 2]. CDK1, 2, 4, and 6 are categorized as cell cycle-related CDKs, coordinating the progression through G1, S, G2, and M phases by phosphorylating key substrates such as the retinoblastoma (Rb) protein [3, 9]. In contrast, CDK9 is a transcriptional CDK that forms part of the positive transcription elongation factor b (P-TEFb) complex, which is essential for RNA polymerase II-mediated transcription elongation [3, 9]. Dysregulation of these kinases is a common feature in many malignancies, where it drives aberrant cell proliferation and survival, making them prominent therapeutic targets in oncology [1, 5]. Therapeutic strategies include the use of selective inhibitors, such as those targeting CDK4/6 for breast cancer, and broader pan-CDK inhibitors like alvocidib (flavopiridol) that target multiple members of this group to induce cell cycle arrest and apoptosis [5, 11]. Despite their clinical potential, the use of CDK inhibitors is often associated with significant safety concerns, including myelosuppression and gastrointestinal toxicities, reflecting the vital roles these enzymes play in normal cellular processes [2, 5].

Other names

Cell cycle-related and transcriptional CDKs [1, 9]Serine/threonine-protein kinases CDK1, CDK2, CDK4, CDK6, and CDK9 [1, 7]CMGC kinases [7]

ATP-competitive inhibition of cyclin-dependent kinases, resulting in cell cycle arrest (G1, S, or G2/M phases) and suppression of RNA polymerase II-mediated transcription elongation [4, 9, 10].