Discovery of Potent and Selective CDK4/6 Inhibitors for the Treatment of Chemotherapy-Induced Myelosuppression

Chemotherapy-induced myelosuppression (CIM) significantly impairs hematopoiesis. Trilaciclib (TC), originally developed for oncology application, is the only FDA-approved CDK4/6 inhibitor for CIM, which effectively protects bone marrow cells by inhibiting their proliferation. In this study, a series of TC derivatives were designed and synthesized as CDK4/6 inhibitors (CDK4/6i) for alleviating CIM. Among these,