BX471

Description: BX471 (also known as ZK-811752) is a novel, oral and non-peptide antagonist of CCR1 (CC chemokine receptor-1) with Ki of 1 nM for human CCR1, and it may be useful in the treatment of chronic inflammatory diseases. BX471 exhibits 250-fold selectivity for CCR1 over CCR2, CCR5 and CXCR4. CCR1 is a prime therapeutic target for treating autoimmune diseases. BX 471 demonstrates a greater than 10, 000-fold selectivity for CCR1 compared with 28 G-protein-coupled receptors. Competition binding studies revealed that BX 471 was able to displace the CCR1 ligands macrophage inflammatory protein-1alpha (MIP-1alpha), RANTES, and monocyte chemotactic protein-3 (MCP-3) with high affinity (K(i) ranged from 1 nm to 5.5 nm). BX 471 was a potent functional antagonist based on its ability to inhibit a number of CCR1-mediated effects including Ca(2+) mobilization, increase in extracellular acidification rate, CD11b expression, and leukocyte migration. Furthermore, BX 471 effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis.

References: J Biol Chem. 2000 Jun 23; 275(25):19000-8.

Related CAS#: 288262-96-4 (HCl); 217645-70-0 (Free base);

ZK811752; ZK 811752; ZK-811752; BX471; BX 471; BX-471

Chemical Name: (R)-1-(5-chloro-2-(2-(4-(4-fluorobenzyl)-2-methylpiperazin-1-yl)-2-oxoethoxy)phenyl)urea