Vaccinia-related kinase 1 (VRK1) (VRK1)

Vaccinia-related kinase 1 (VRK1) is a member of the serine/threonine kinase family that plays a pivotal role in regulating the cell cycle, DNA damage response, and nuclear envelope assembly (UniProt P49759). By phosphorylating a diverse array of substrates such as p53, histone H3, and BAF, VRK1 coordinates essential nuclear functions and maintains genomic integrity (PubMed: 30333210). The protein is frequently upregulated in numerous cancers, including breast, lung, and colon carcinomas, where it promotes tumor growth and resistance to therapy (PubMed: 32824818). This overexpression makes VRK1 a promising target for small-molecule inhibitor development, especially in the context of precision medicine and synthetic lethality. However, its critical role in normal physiology is underscored by the fact that mutations in the VRK1 gene are associated with rare neurodegenerative disorders like spinal muscular atrophy and pontocerebellar hypoplasia (PubMed: 21445321). Therapeutic development must therefore balance potent anti-tumor activity with the potential for neurological or systemic toxicity.

Other names

Vaccinia-related kinase 1VRK serine/threonine kinase 1Serine/threonine-protein kinase VRK1PCH1A

ATP-competitive inhibition of the kinase domain to prevent phosphorylation of downstream substrates.