compound-1308

Compound-1308 is a small-molecule dual inhibitor of cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 2 (CDK2). It was developed to address clinical challenges associated with first-generation CDK4/6 inhibitors, specifically hematologic toxicities mediated by CDK6 inhibition and acquired drug resistance driven by cyclin E/CDK2 activation. Preclinical data indicates that Compound-1308 possesses a long residence time on CDK2 and demonstrates superior antiproliferative activity in palbociclib- and abemaciclib-resistant breast cancer cell lines and patient-derived xenograft (PDX) models. Furthermore, it shows a reduced impact on human primary hematopoietic stem and precursor cells compared to palbociclib, suggesting a wider therapeutic window with potentially less myelosuppression.