Description
NBI 74330 is a chemokine (C-X-C motif) receptor 3 (CXCR3) antagonist (K
i = 3.6 nM in a radioligand binding assay). It inhibits calcium mobilization induced by chemokine (C-X-C motif) ligand 10 (CXCL10) or CXCL11 in RBL cells expressing human CXCR3 (IC
50 = 7 nM for both). NBI 74330 inhibits CXCL11-induced chemotaxis of CXCR3-expressing H9 cells and PHA and IL-2 differentiated T cells (IC
50s = 3.9 and 6.6 nM, respectively).
In vivo, NBI 74330 (100 mg/kg) reduces peritoneal lymphocyte migration in a mouse model of peritonitis. It reduces the size and number of aortic arch atherosclerotic lesions in
Ldlr-/- mice. NBI 74330 reduces spinal cord microglial activation and levels of CXCL4, CXCL9, and CXCL10 and decreases thermal and mechanical hyperalgesia in a rat model of chronic constriction injury-induced neuropathic pain.
Uses
N-[(1R)-1-[3-(4-Ethoxyphenyl)-3,4-dihydro-4-oxopyrido[2,3-d]pyrimidin-2-yl]ethyl]-4-fluoro-N-(3-pyridinylmethyl)-3-(trifluoromethyl)benzeneacetamide is a CXCR3 antagonist.
