cyclin dependent kinase 1

Overview

Cyclin dependent kinase 1 (CDK1) is a core serine/threonine protein kinase that plays a central role in cell-cycle control, particularly the transition into and progression through mitosis. In normal biology, CDK1 functions as part of the cyclin-dependent kinase network that coordinates DNA replication, checkpoint control, and cell division. Its activity is tightly regulated by cyclins and by inhibitory phosphorylation events, reflecting its importance as a gatekeeper of proliferative progression.

In biomedical research, CDK1 is widely studied as an anticancer target because many tumors depend on dysregulated cell-cycle machinery for continued growth. Recent studies have also linked CDK1 to DNA damage responses and signaling pathways beyond canonical mitotic control, including cGAS-STING-related immune activation and checkpoint kinase regulation. These findings place CDK1 at the intersection of cell-cycle biology, genome stability, and therapeutic vulnerability in cancers such as nasopharyngeal carcinoma, hepatocellular carcinoma, lymphoma, and other invasive malignancies.

Focus of Latest Publications

Recent publications on cyclin-dependent kinase 1 (CDK1) have focused heavily on its role as a cell-cycle regulator and therapeutic target in cancer, with multiple studies using computational, chemical, and in vivo approaches to evaluate CDK1-directed interventions. Several reports described the design and optimization of selective small-molecule CDK1 inhibitors, including pyrazolopyrimidine and 1,2,4-triazolobenzene sulfonamide scaffolds. In these studies, molecular docking, 3D-QSAR modeling, molecular dynamics simulations, and ADMET profiling were used to identify compounds with strong predicted binding and favorable drug-like properties. One triazolobenzene sulfonamide lead, 11l, showed nanomolar CDK1 inhibition, high selectivity over CDK2, Aurora A, and Cdk4, induced G2/M arrest, and triggered DNA replication stress with activation of p53 signaling and apoptosis, while also demonstrating in vivo antitumor activity without obvious toxicity.

Other recent work linked CDK1 to broader oncogenic and immune-related pathways. A pan-cancer multi-omics analysis identified CDK1 as a hub target alongside AURKA and CCNB1 in breast, ovarian, and colorectal cancers, and suggested that AMG-900 may bind CDK1 with favorable affinity, although molecular dynamics indicated comparatively reduced stability for the CDK1 complex relative to some other targets. In pancreatic cancer, an in vivo CRISPR-Cas9 screen identified the CDK1/Cyclin B1 complex as a tumor-intrinsic driver of immune evasion; genetic or pharmacologic inhibition of this complex promoted a T cell-inflamed tumor microenvironment and enhanced responses to PD-1 blockade. Mechanistically, loss of Cyclin B1 reduced Rb phosphorylation, restored NF-κB activity, increased Csf2 production, and supported dendritic cell recruitment and activation.

CDK1 was also studied in the context of vascular disease and DNA damage response. In a mouse model of carotid artery injury, elafibranor reduced neointima formation and suppressed vascular smooth muscle cell proliferation, migration, and phenotypic switching; transcriptomic analyses implicated cell-cycle control pathways, and the study specifically showed that elafibranor downregulated CDK1, with CDK1 overexpression reversing these inhibitory effects. In nasopharyngeal carcinoma, a ROS-sensitive nanoparticle co-delivering a platinum(IV) prodrug and the CDK1 inhibitor RO-3306 was designed to enhance chemo-immunotherapy by blocking CDK1-driven DNA repair and CDK1-mediated cGAS phosphorylation, thereby amplifying cGAS-STING signaling and antitumor immunity. Together, these publications portray CDK1 as a central node in proliferation, checkpoint control, DNA repair, and tumor immune regulation, and they highlight ongoing efforts to exploit CDK1 inhibition for anticancer and other disease-modifying strategies.