855527-92-3

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 (IC₅₀ = 7 nM for both). NBI 74330 inhibits CXCL11-induced chemotaxis of CXCR3-expressing H9 cells and PHA and IL-2 differentiated T cells (IC₅₀s = 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.

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.

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

[1] CHRISTOPHER E HEISE. Pharmacological characterization of CXC chemokine receptor 3 ligands and a small molecule antagonist.[J]. Journal of Pharmacology and Experimental Therapeutics, 2005, 313 3: 1263-1271. DOI: 10.1124/jpet.105.083683
[2] EVA J A VAN WANROOIJ. CXCR3 antagonist NBI-74330 attenuates atherosclerotic plaque formation in LDL receptor-deficient mice.[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2008: 251-257. DOI: 10.1161/atvbaha.107.147827
[3] ANNA PIOTROWSKA . Pharmacological blockade of CXCR3 by (±)-NBI-74330 reduces neuropathic pain and enhances opioid effectiveness - Evidence from in vivo and in vitro studies[J]. Biochimica et biophysica acta. Molecular basis of disease, 2018, 1864 10: Pages 3418-3437. DOI: 10.1016/j.bbadis.2018.07.032