AL-0433

AL-0433 is a novel, selective, and brain-penetrant small molecule inhibitor of cyclin-dependent kinase 4 (CDK4). Developed by Expert Systems using AI-driven virtual screening and structure-based design, it demonstrates approximately 30-fold selectivity for CDK4 over CDK6, and over 1000-fold selectivity over other CDKs such as CDK1, CDK2, and CDK9. By specifically targeting CDK4, AL-0433 aims to inhibit tumor cell proliferation while sparing CDK6-dependent hematopoiesis, potentially avoiding the neutropenia associated with non-selective CDK4/6 inhibitors. Its high blood-brain barrier permeability makes it a promising candidate for treating glioblastoma and brain metastases. Preclinical data show potent activity in breast and ovarian cancer models, as well as inhibition of pRB phosphorylation.