CC-292 + methotrexate

**CC-292 + methotrexate** is a combination regimen consisting of CC-292, a small molecule inhibitor of Bruton’s tyrosine kinase (Btk), and methotrexate, a widely-used disease-modifying antirheumatic drug (DMARD). CC-292 inhibits Btk activity by irreversible covalent binding to the ATP binding site found on Btk, which disrupts B cell receptor signaling and subsequent inflammatory processes relevant to autoimmune diseases. Methotrexate is an antifolate and antimetabolite that inhibits dihydrofolate reductase (DHFR), blocking nucleotide synthesis and immune cell proliferation; it also exerts immunomodulatory effects through multiple mechanisms. The CC-292 + methotrexate combination has been investigated in clinical studies for rheumatoid arthritis unresponsive to methotrexate alone[1].