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.

Key Publications

NEWJun Molecular modeling of highly selective CDK1 Inhibitors based on pyrazolo-pyrimidines using 3D-QSAR, docking, and molecular dynamics simulations. (PloS one, 2026, PMID 42329991): "Cyclin-dependent kinase 1 (CDK1) has emerged as a compelling target for anticancer drug development due to its essential role in cell cycle regulation."
Jun Multi-omics and pan-cancer analysis revealed common molecular signatures to disclose multitargeted anticancer agents through network pharmacology approach. (PloS one, 2026, PMID 42224282): "The protein-protein interaction (PPI) network study reveals the top-ranked, most significant hub targets, AURKA, CDK1 and CCNB1, as drug targets."
May Elafibranor inhibits neointima formation by downregulating CDK1 expression in carotid artery injury mice model. (European journal of pharmacology, 2026, PMID 42150712): "In particular, it downregulated cyclin-dependent kinase 1 (CDK1), a key regulator of the G2/M checkpoint."
May Integrating network toxicology with multi-omics approaches to elucidate molecular targets and pathway mechanisms in BPA-induced hepatocellular carcinoma. (Molecular diversity, 2026, PMID 42118483): "Six hub genes (MKI67, CCNA2, EZH2, CCNB1, CDK1, BIRC5) were significantly upregulated in HCC with high internal cross-validated diagnostic accuracy (AUC > 0.96), although these estimates may be susceptible to overfitting and require external validation."
May Discovery of Naphthyridinone Derivatives as Selective PKMYT1/WEE1 Dual Inhibitors for Cancer Therapy. (Journal of medicinal chemistry, 2026, PMID 42003565): "Dual inhibition of PKMYT1 and WEE1, key G2/M checkpoint kinases that phosphorylate CDK1 at T14 and Y15, offers a strategy for tumors with abrogated G1/S checkpoint and high replication stress."
Jun Oncolytic human adenovirus 5 (H101) modulates cell cycle progression in HPV16-positive tumors. (Biochemical and biophysical research communications, 2026, PMID 42000628): "At the molecular level, H101 downregulated HPV16 E6/E7 expression, thereby activating the p53-p21 signaling axis and inhibiting CDK1 phosphorylation."
Jun Targeting DNA repair with a Pt(IV) prodrug nanoparticle potentiates chemo-immunotherapy for nasopharyngeal carcinoma through cGAS-STING activation. (Journal of controlled release : official journal of the Controlled Release Society, 2026, PMID 41966338): "RO-3306 blocks CDK1-driven DNA repair and prevents CDK1-mediated cGAS phosphorylation, amplifying cisplatin-induced DNA damage and enhancing cGAS activity."
Mar Targeting tumor-intrinsic CDK1/Cyclin B1 complex improves responses to immunotherapy in pancreatic cancer. (Cancer letters, 2026, PMID 41921857): "...identified the CDK1/Cyclin B1 complex as a previously unrecognized tumor-intrinsic driver of immune evasion in pancreatic cancer."
Jun Design and synthesis of novel 1,2,4-triazolobenzene sulfonamide derivatives as selective CDK1 inhibitors with potent in vivo anticancer efficacy. (European journal of medicinal chemistry, 2026, PMID 41903286): "Cyclin-dependent kinase 1 (CDK1) is a key regulator of cell cycle progression and a potential therapeutic target for invasive malignancies."