SCH 546738 is an orally available, selective and potent CXCR3 antagonist that attenuates the development of autoimmune diseases and delays graft rejection.

CXCR3 (human):0.4 nM (Ki), CXCR3-mediated chemotaxis (human activated T cells):10 nM (IC90)

SCH 546738 effectively and specifically inhibits CXCR3-mediated chemotaxis in human activated T cells (IC90=10 nM). SCH 546738 displaces radiolabeled CXCL10 and CXCL11 from human CXCR3 (IC50: ranging from 0.8 to 2.2 nM) in a non-competitive manner. Competition of human CXCL10 and CXCL11 binding to human CXCR3 by SCH 546738 is determined at various concentrations of [125I]hCXCL10 and [125I]hCXCL11 around the Kd (50-100 pM) for the receptor. [1]

SCH 546738 is a selective and effective CXCR3 antagonist with a good PK for in vivo studies. SCH 546738 has a favorable pharmacokinetic profile in rodents, the plasma concentrations of SCH 546738 in Lewis rat, and C57BL/6 mouse over 24 hr post-dose. SCH 546738 has strong cross-species activities in inhibiting the binding of [125I]hCXCL10 to CXCR3 of monkey (IC50 = 1.3 nM), dog (IC50 = 6.4 nM), mouse (IC50 = 5.9 nM) and rat origin (IC50 = 4.2 nM). [1]