BX-471

Cas：217645-70-0 (free base)

Product Information：

BX-471, also known as ZK-811752, is a potent, selective non-peptide CCR1 antagonist (Ki = 1 nM for human CCR1). BX-471 exhibits 250-fold selectivity for CCR1 over CCR2, CCR5 and CXCR4. BX-471 was developed Berlex and its parent company, Schering AG. BX-471 is the lead in a series of non-peptide chemokine receptor 1 (CCR1) antagonists, for the potential treatment of autoimmune diseases, in particular multiple sclerosis (MS). In March 2000, BX-471 was undergoing phase I trials for the potential treatment of autoimmune diseases.

Chemical Formula: C21H24ClFN4O3

Exact Mass: 434.1521

Molecular Weight: 434.89

Elemental Analysis: C, 58.00; H, 5.56; Cl, 8.15; F, 4.37; N, 12.88; O, 11.04

Synonym: 

BX471

BX 471

BX-471

ZK811752

ZK 811752

ZK-811752

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

InChi Key: 

XQYASZNUFDVMFH-CQSZACIVSA-N

InChi Code: InChI=1S/C21H24ClFN4O3/c1-14-11-26(12-15-2-5-17(23)6-3-15)8-9-27(14)20(28)13-30-19-7-4-16(22)10-18(19)25-21(24)29/h2-7,10,14H,8-9,11-13H2,1H3,(H3,24,25,29)/t14-/m1/s1

Smiles Code:

C[C@H]1N(C(COC2=CC=C(Cl)C=C2NC(N)=O)=O)CCN(CC3=CC=C(F)C=C3)C1

Technical Data：

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

In Vitro：

BX471 is a potent functional antagonist based on its ability to inhibit a number of CCR1-mediated effects including Ca2+ 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 125I-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 Ca2+ 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 lymphocytes to activated endothelium.

In Vivo：

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.

References：

1. Vandemeulebroecke M, Lembcke J, Wiesinger H, Sittner W, Lindemann S. Assessment of QT(c)-prolonging potential of BX471 in healthy volunteers. A 'thorough QT study' following ICH E14 using various QT(c) correction methods. Br J Clin Pharmacol. 2009 Sep;68(3):435-46. doi: 10.1111/j.1365-2125.2009.03460.x. PubMed PMID: 19740402; PubMed Central PMCID: PMC2766484.

2. He M, Horuk R, Bhatia M. Treatment with BX471, a nonpeptide CCR1 antagonist, protects mice against acute pancreatitis-associated lung injury by modulating neutrophil recruitment. Pancreas. 2007 Mar;34(2):233-41. PubMed PMID: 17312463.

3. He M, Horuk R, Moochhala SM, Bhatia M. Treatment with BX471, a CC chemokine receptor 1 antagonist, attenuates systemic inflammatory response during sepsis. Am J Physiol Gastrointest Liver Physiol. 2007 Apr;292(4):G1173-80. Epub 2007 Jan 18. Erratum in: Am J Physiol Gastrointest Liver Physiol. 2012 Jan;302(1):G194. PubMed PMID: 17234893.

4. Horuk R. BX471: a CCR1 antagonist with anti-inflammatory activity in man. Mini Rev Med Chem. 2005 Sep;5(9):791-804. Review. PubMed PMID: 16178722.

Products are for research use only. Not for human use.