NBI-74330

NBI-74330 is a potent antagonist for CXCR3 , and exhibits potent inhibition of ( 125 I)CXCL10 and ( 125 I)CXCL11 specific binding with K i of 1.5 and 3.2 nM, respectively.

In Vitro

BI-74330 demonstrates potent inhibition of [ 125 I]CXCL11 specific binding to membranes prepared from transfected CHO cells expressing CXCR3 (CXCR3-CHO) (K i =3.6 nM). NBI-74330 is 12- and 3.5-fold more potent than CXCL9 (K i =45.2 nM) and CXCL10 (K i =12.5 nM), respectively, at inhibiting [ 125 I]CXCL11 binding to CXCR3-CHO cell membranes. NBI-74330 inhibits calcium mobilization in response to CXCL11 and CXCL10 with an IC 50 value of 7 nM for both ligands used at their EC 80 concentrations (1 nM for CXCL11 and 30 nM for CXCL10). NBI-74330 specifically inhibits CXCR3-mediated calcium mobilization. NBI-74330 also dose-dependently inhibits CXCL11-induced [ 35 S]GTPγS binding in membranes of cells endogenously expressing CXCR3 (H9 cells, IC 50 value 5.5 nM). BI-74330 inhibits CXCL11-induced chemotaxis in these cells with an IC 50 of 3.9 nM. NBI-74330 (30-300 nm, 1-10 μM) produces concentration-dependent, parallel rightward shifts of the CXCL11 E/[A] curve with no significant change in the E/[A] curve maximal response. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

NBI-74330 (100 mg/kg) results in the formation of an N-oxide metabolite, also an antagonist of CXCR3, in mice. Mice treated with 100 mg/kg NBI-74330 (in 1% Na Doc in 0.5% 400Cp Methylcellulose) result in serum concentrations of approximately 1 μM. This concentration is sufficient to fully block the CXCR3 receptor in vivo. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Form:Solid

IC50& Target:[ 125 I]CXCL10-CXCR3 1.5 nM (Ki, in CXCR3-CHO cell membranes) [ 125 I]CXCL11-CXCR3 3.2 nM (Ki, in CXCR3-CHO cell membranes)