CCR1 antagonist,potent and selective
CAS：217645-70-0
分子式：C21H24ClFN4O3
分子量：434.89
纯度：98%
存储：Store at -20°C

Background:

Ki: 1 nM to 5.5 nM

The CC chemokine receptor-1 (CCR1) is a prime therapeutic target for treating autoimmune diseases. BX 471 is a potent, selective, and orally active antagonist of the CC Chemokine Receptor-1.

In vitro: Competition binding studies revealed that BX 471 was able to displace the CCR1 ligands macrophage inflammatory protein-1a, RANTES, and monocyte chemotactic protein-3 with high affinity. BX 471 was a potent functional antagonist based on its ability to inhibit plenty of CCR1-mediated effects. BX 471 also demonstrated a greater than 10,000-fold selectivity for CCR1 compared with 28 G-protein-coupled receptors [1].

In vivo: Pharmacokinetic studies demonstrated that BX 471 was orally active with a 60% bioavailability in dogs. Furthermore, in a rat experimental allergic encephalomyelitis model of multiple sclerosis, BX 471 effectively reduces disease [1].

Clinical trial: Up to now, BX 471 is still in the preclinical development stage.

Reference:
[1] Liang M, Mallari C, Rosser M, Ng HP, May K, Monahan S, Bauman JG, Islam I, Ghannam A, Buckman B, Shaw K, Wei GP, Xu W, Zhao Z, Ho E, Shen J, Oanh H, Subramanyam B, Vergona R, Taub D, Dunning L, Harvey S, Snider RM, Hesselgesser J, Morrissey MM, Perez HD.  Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1. J Biol Chem. 2000 Jun 23;275(25):19000-8.