Bruton’s tyrosine kinase (BTK) is a non-receptor tyrosine kinase involved in signal transduction pathways regulating the proliferation, activation, and differentiation of B cells. AVL-292 is an orally available, selective, and irreversible inhibitor of BTK (IC50 = 0.5 nM in vitro in B cell lymphoma cell lines) that targets and covalently binds to BTK at cysteine-481, thereby preventing its activity. AVL-292 has been shown to inhibit osteoclast function and to reduce osteoclast-stimulated proliferation of multiple myeloma cells in animal models of rheumatoid arthritis and multiple sclerosis, both of which are diseases where B cells play an important role. In clinical trials, AVL-292 has demonstrated therapeutic significance in the treatment of both B cell-related cancers (e.g., non-Hodgkin’s lymphoma and B cell chronic lymphocytic leukemia) and autoimmune diseases (e.g., rheumatoid arthritis).
