GDC-0587

GDC-0587 is an orally bioavailable, selective small molecule inhibitor of cyclin-dependent kinase 4 (CDK4), currently under development by Genentech (a member of the Roche Group). Unlike first-generation CDK4/6 inhibitors such as palbociclib and ribociclib, which inhibit both CDK4 and CDK6, GDC-0587 is designed to be more selective for CDK4. This selectivity is intended to minimize hematological toxicities, such as neutropenia, which are primarily driven by CDK6 inhibition in the bone marrow, while maintaining potent anti-tumor activity in CDK4-dependent cancers. The drug is primarily being investigated for the treatment of estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, particularly in patients who have previously progressed on or after treatment with standard CDK4/6 inhibitors. It is being evaluated both as a monotherapy and in combination with other endocrine therapies, such as the selective estrogen receptor degrader (SERD) giredestrant.