BX471 hydrochloride (ZK-811752 hydrochloride) 是以一种有效的，选择性的，非肽段的 CCR1 拮抗剂，抑制人 CCR1 活性，K_i 值为 1 nM，对其选择性是对 CCR2，CCR5 和 CXCR4 的 250 倍。

BX471 hydrochloride (ZK-811752 hydrochloride) is a potent, selective non-peptide CCR1 antagonist with K i of 1 nM for human CCR1, and exhibits 250-fold selectivity for CCR1 over CCR2, CCR5 and CXCR4.

Solid

MIP-1α-CCR1 1 nM (Ki) RANTES-CCR1 2.8 nM (Ki)

BX471 is a potent functional antagonist based on its ability to inhibit a number of CCR1-mediated effects including Ca mobilization, increase in extracellular acidification rate, CD11b expression, and leukocyte migration. BX471 demonstrats a greater than 10,000-fold selectivity for CCR1 compared with 28 G-protein-coupled receptors. BX471 is also able to displace I-MIP-1α/CCL3 binding to mouse CCR1 in a concentration-dependent manner with a Ki of 215±46 nM. Increasing concentrations of BX471 inhibits the Ca transients induced by MIP-1α/CCL3 in both human and mouse CCR1 with IC50 of 5.8±1 nM and 198±7 nM, respectively. BX471 (0.1-10 μM) shows a dose-dependent inhibition of RANTES-mediated and shear-resistant adhesion on IL-1β-activated microvascular endothelium in shear flow in isolated blood monocytes. BX471 also inhibits the RANTES-mediated adhesion of T

BX471 (4 mg/kg, p.o. or i.v.) is orally active with a bioavailability of 60% in dogs. Furthermore, BX471 effectively reduces disease in a rat experimental allergic encephalomyelitis model of multiple sclerosis. BX471 (20 mg/kg, s.c.) reaches peak plasma levels of 9 μM by around 30 minutes, and this rapidly declines to approximately 0.4 μM after 2 hours. From 4 to 8 hours the drug plasma levels drops to 0.1 μM or lower. Mice treated with 20 mg/kg of BX471 for 10 days shows a reduction of interstitial CD45 positive leukocytes of approximately 55%. BX471 has a borderline significant effect on the number of CCR5-positive CD8 cells in the peripheral blood. BX471 reduces the amount of FSP1-positive cells by 65% in UUO kidneys as compared with vehicle control. Pretreatment witih BX471 reduces macrophage and neutrophil accumulation in kidney after ischemia-reperfusion injury.

Room temperature in continental US; may vary elsewhere.

-20°C, sealed storage, away from moistur In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

[1]. Liang M, et al. 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.
[2]. Anders HJ, et al. A chemokine receptor CCR-1 antagonist reduces renal fibrosis after unilateral ureter ligation. J Clin Invest. 2002 Jan;109(2):251-9.

In Vitro: DMSO : 150 mg/mL (318.23 mM; Need ultrasonic)H₂O : < 0.1 mg/mL (ultrasonic) (insoluble)配制储备液