SCH 546738 is a novel, potent and non-competitive small molecule CXCR3 antagonist with Ki of 0.4 nM .
SCH 546738 at 10 nM inhibited T cell chemotaxis induced by all three CXCR3 ligands about 90%. In multiple experiments, the affinity constant (Ki) of SCH 546738 binding to human CXCR3 receptor was determined to be 0.4 nM. The IC50 of SCH 546738 is constant (~1 or 2 nM) and independent of the input concentrations of either [125I]hCXCL10 (25-500 pM) or [125I]hCXCL11 (12.5-250 pM), respectively. SCH 546738 has strong cross-species activities with IC50 of 1.3 nM, 6.4 nM, 5.9 nM and 4.2 nM in inhibiting the binding of [125I]hCXCL10 to CXCR3 of monkey, dog, mouse and rat origin, respectively .