PF-7006

PF-7006 is a highly selective, extremely potent small molecule inhibitor of monopolar spindle 1 (Mps1) kinase, also known as dual specificity protein kinase TTK, with a Ki of 0.27 nM. Developed by Pfizer, PF-7006 targets the mitotic checkpoint (spindle assembly checkpoint) to induce genomic instability and mitotic catastrophe in cancer cells. In preclinical models, PF-7006 has demonstrated significant tumor growth inhibition, particularly in triple-negative breast cancer (TNBC) models. However, its clinical utility as a single agent is limited by dose-limiting toxicities such as body weight loss, gastrointestinal toxicities, and neutropenia. Preclinical studies suggest these toxicities may be mitigated, and efficacy enhanced, when combined with CDK4/6 inhibitors like palbociclib, particularly in Rb1-deficient tumors.