BMS-817399 + methotrexate

BMS-817399 + methotrexate is a **combination therapy** comprising BMS-817399, a selective, orally bioavailable antagonist of the C-C chemokine receptor type 1 (CCR1), and methotrexate, a folate antimetabolite and immunosuppressant. BMS-817399 was developed as a urea-based small molecule intended to modulate inflammatory responses by inhibiting CCR1, a receptor implicated in leukocyte trafficking and the pathogenesis of rheumatoid arthritis. Methotrexate is a standard antirheumatic drug that inhibits dihydrofolate reductase, suppressing DNA synthesis and cell proliferation, and is widely used in autoimmune conditions including rheumatoid arthritis. In clinical studies, the combination has been evaluated for the treatment of **moderate to severe rheumatoid arthritis**, aiming to leverage complementary mechanisms—blocking chemokine-mediated cell migration while inhibiting immune cell proliferation and function.