Venetoclax is a potent, selective inhibitor of B-cell lymphoma (BCL)-2, an anti-apoptotic protein. Overexpression of BCL-2 has been shown to be observed in leukemic cells from patients with chronic lymphocytic (lymphoid) leukemia (CLL), where it mediates tumor cell survival and is associated with resistance to chemotherapy.
Venetoclax binds directly to the BH3-binding groove of BCL-2 proteins, displacing proapoptotic proteins and triggering the process of increased mitochondrial outer membrane permeability (MOMP), caspase activation, and programmed cell death. In preclinical studies, venetoclax has been shown to be toxic to tumor cells that overexpress BCL-2.
Cmax of venetoclax in plasma was achieved after 5-8 hours. AUC increased proportionally to the dose in the range of 150-800 mg. Venetoclax has a high degree of binding to plasma proteins within the concentration range of 1-30 μM (0.87-26 μg/ml). Volume of distribution - 256-321 L. T½ - 26 hours.
