bgb-43395

BGB-43395 is a highly potent and selective small molecule inhibitor of cyclin-dependent kinase 4 (CDK4), developed as an antineoplastic agent for the treatment of advanced solid tumors, including hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Unlike dual CDK4/6 inhibitors, which are associated with dose-limiting neutropenia due to CDK6 inhibition, BGB-43395 is engineered to selectively inhibit CDK4 while sparing CDK6. This selectivity aims to reduce hematological toxicity and allow for more consistent drug exposure. Mechanistically, BGB-43395 inhibits phosphorylation of retinoblastoma protein (Rb) early in the G1 phase of the cell cycle, preventing G1-S transition and leading to cell cycle arrest and suppression of tumor proliferation. Preclinical studies have shown robust activity in both monotherapy and combination settings—including models resistant to existing CDK4/6 inhibitors—and a favorable safety profile with low rates of neutropenia. The drug is currently being evaluated in phase 1 clinical trials as monotherapy or in combination with endocrine therapies such as fulvestrant or letrozole for HR+/HER2− breast cancer and other advanced solid tumors[1][5][6][8].

Other names

BGB 43395BGB43395BGB-43395CDK4 inhibitor BGB-43395CDK-4 inhibitor BGB-43395CDK 4 inhibitor BGB-43395