BX 471

The CC chemokine receptor-1 (CCR1), whose ligands include macrophage inflammatory protein-1α (MIP-1α), RANTES, and monocyte chemotactic protein-3 (MCP-3), has a central role in leukocyte trafficking and is highly expressed in certain autoimmune diseases. BX 471 is a nonpeptide CCR1 antagonist that has been shown to displace MIP-1α, RANTES, and MCP-3 with K_i values of 1, 2.8, and 5.5 nM, respectively.¹ It demonstrates >10,000-fold selectivity for CCR1 over 28 additional G protein-coupled receptors, including related chemokine receptors.¹ In a rat experimental allergic encephalomyelitis model of multiple sclerosis, BX 471 at 50 mg/kg was shown to significantly reduce the severity of the disease.¹ BX 471 also decreases the inflammatory response during sepsis, blocks migration of monocytes isolated from rheumatoid arthritis patients, and prevents macrophage and T-cell recruitment in a mouse model of lupus nephritis.^2,3,4

WARNING This product is not for human or veterinary use.

1. Liang, M., Mallari, C., Rosser, M., et al. Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1. The Journal of Biological Chemisty 275(25), 19000-19008 (2000).

2. He, M., Horuk, R., Moochhala, S., et al. Treatment with BX471, a CC chemokine receptor 1 antagonist, attenuates systemic inflammatory response during sepsis. Am. J. Physiol. Gastrointest. Liver Physiol. 292(4), G1173-G1180 (2007).

3. Lebre, M.C., Vergunst, C.E., Choi, I.Y.K., et al. Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis. PLoS One 6(7), (2011).

4. Anders, H.J., Belemezova, E., Eis, V., et al. Late onset of treatment with a chemokine receptor CCR1 antagonist prevents progression of lupus nephritis in MRL-Fas(lpr) mice. J. Am. Soc. Nephrol. 15(6), 1504-1513 (2004).