CMP3a

CMP3a (Compound 3a) is a selective small-molecule inhibitor of NIMA-related kinase 2 (NEK2), specifically designed to target the NEK2-EZH2 signaling axis in glioblastoma (GBM). In glioma stem cells (GSCs), NEK2 binds to and phosphorylates the epigenetic regulator EZH2, protecting it from ubiquitination-dependent proteasomal degradation. By inhibiting NEK2 kinase activity, CMP3a triggers EZH2 degradation, which leads to reduced GSC clonogenicity and impaired tumor propagation. Preclinical studies have demonstrated that CMP3a effectively attenuates GBM growth in mouse models and exhibits a synergistic effect when combined with radiotherapy, suggesting its potential as a therapeutic agent for recurrent and radioresistant glioblastoma.