ZMS-7506

ZMS-7506 is a potent, orally bioavailable small molecule inhibitor of Cyclin A and Cyclin B, developed for the treatment of cancers characterized by dysregulated E2F activity, such as small cell lung cancer (SCLC) and ovarian cancer. By disrupting the interaction between E2F and the cyclin A2-CDK2 complex, ZMS-7506 induces hyperactivation of E2F, leading to synthetic lethality and apoptosis. The compound triggers G2/M cell cycle arrest and activates the spindle assembly checkpoint (SAC), as indicated by increased phosphorylation of KNL1, histone H3, PARP, and γ-H2AX. Pre-clinical data demonstrate significant anti-proliferative activity in SCLC and OVCAR3 cell lines with a favorable safety profile in normal fibroblasts, alongside robust in vivo efficacy in xenograft models.