Polo-like kinase 2 (PLK2), Proto-oncogene tyrosine-protein kinase Src (Src), Cyclin-dependent kinase 1 (CDK1), and Tyrosine-protein kinase Fyn (Fyn) (PLK2, Src, CDK1, Fyn)

The target set "PLK2, Src, Cdk1, Fyn" refers to a group of four distinct protein kinases: Polo-like kinase 2 (PLK2), Proto-oncogene tyrosine-protein kinase Src (Src), Cyclin-dependent kinase 1 (CDK1), and Tyrosine-protein kinase Fyn (Fyn). These enzymes are critical regulators of the cell cycle, signal transduction, and neuronal homeostasis (UniProt; PMC, 2025). PLK2 and CDK1 are primarily involved in mitotic entry and progression, while Src and Fyn are non-receptor tyrosine kinases that mediate signaling from various surface receptors to control cell growth and survival (PubMed, 2023). This specific combination of kinases is notably identified as the secondary target profile of the multi-kinase inhibitor rigosertib (ON-01910.Na), which primarily targets PLK1 but exhibits significant affinity for these four enzymes (Theranostics, 2021; MDPI, 2023). Dysregulation of these kinases is frequently observed in various malignancies, including leukemias and solid tumors, as well as in neurodegenerative conditions like Parkinson's disease, where they contribute to pathological protein phosphorylation (bioRxiv, 2023; PMC, 2025). Therapeutic targeting of this group aims to induce mitotic arrest and apoptosis in malignant cells or modulate pathological protein phosphorylation in neurons (Pharmaceutical Sciences, 2021). However, broad inhibition of these essential kinases can lead to significant safety concerns, including myelosuppression and gastrointestinal toxicity (NIH, 2022).

Other names

SNKSerum-inducible kinasep60-Srcc-SrcCDC2Cell division control protein 2 homologp59-FynSLKRigosertib target profile

Inhibition of kinase catalytic activity, leading to mitotic arrest, disruption of oncogenic signaling pathways (e.g., Ras/MAPK), and induction of apoptosis.