ABK-CDK4

ABK-CDK4 is a highly selective and brain-penetrant small molecule inhibitor of cyclin-dependent kinase 4 (CDK4), developed by Abbisko Therapeutics. Unlike first-generation dual CDK4/6 inhibitors such as palbociclib, ABK-CDK4 demonstrates over 70-fold selectivity for CDK4 over CDK6. This selectivity is intended to reduce dose-limiting hematological toxicities associated with CDK6 inhibition while maintaining robust anti-tumor efficacy. The compound is specifically designed to cross the blood-brain barrier (Kpuu > 0.5), making it a potential therapeutic option for patients with HR+/HER2- breast cancer, particularly those with brain metastases. Preclinical studies have shown effective suppression of retinoblastoma (Rb) phosphorylation and tumor growth inhibition in xenograft models.