BX471

BX471 (ZK811752, BAY 865047, SH T 04268H) is a potent nonpeptide CC chemokine receptor-1 (CCR1) antagonist with Ki values of 1 nM and 5.5 nM in both MIP-1α and MCP-3 binding to CCR1-transfected HEK293 cells, respectively.

By displacing the ligand binding to CC chemokine receptor-1 (CCR1), BX 471, a potent antagonist, can inhibit the effects medicated by CCR1. In addition, BX-471 exhibits anti-allergic effect by increasing Treg cell population.^{<a class="sref" href="#s_ref">[1]</a>}^{<a class="sref" href="#s_ref">[2]</a>}

For fasted dogs, the half-life for BX 471 was approximately 3 h, with an oral bioavailability of approximately 60%. In rats of EAE model, CCR1 antagonist, BX 471, dose-dependently decreased the severity of the disease.^{<a class="sref" href="#s_ref">[1]</a>}

• Cell lines

  THP-1- or CCR1-transfected HEK293 cells

• Concentrations

  10 µM

• Incubation Time

  24 h

• Method

  Binding assays were performed by filtration. Radiolabeled chemokines at a final concentration of approximately 0.1–0.2 nM were used as ligand. HEK293 cells expressing human CCR1 at 8,000 or 300,000 cells per assay point were used as the receptor source. Nonspecific binding was determined in the presence of 100 nM unlabeled chemokine. The binding data were curve-fitted with the computer program IGOR (Wavemetrics) to determine the affinity and number of sites. To demonstrate that CCR1 antagonism by BX 471 was not due to the cellular toxicity of the compound, THP-1- or CCR1-transfected HEK293 cells were treated with BX 471 at concentrations up to 10 µM for 24 h, and cellular toxicity was monitored by measuring WST-1 staining. No significant toxicity was observed.

• Animal Models

  Fasted male beagle dogs; Male Lewis Rats of EAE model

• Dosages

  4 mg/kg (for fasted male beagle dogs); 20 and 50 mg/kg (for Male Lewis Rats)

• Administration

  p.o.