| Identification | Back Directory | [Name]
NBI-74330 | [CAS]
855527-92-3 | [Synonyms]
NBI-74330
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
Benzeneacetamide, 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)- | [Molecular Formula]
C32H27F4N5O3 | [MDL Number]
MFCD11850718 | [MOL File]
855527-92-3.mol | [Molecular Weight]
605.58 |
| Chemical Properties | Back Directory | [Boiling point ]
752.5±70.0 °C(Predicted) | [density ]
1.32±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:100.0(Max Conc. mg/mL);165.1(Max Conc. mM) | [form ]
Powder | [pka]
4?+-.0.11(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Description]
NBI 74330 is a chemokine (C-X-C motif) receptor 3 (CXCR3) antagonist (Ki = 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. | [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. | [in vivo]
NBI-74330 (100 mg/kg) results in the formation of an N-oxide metabolite, also an antagonist of CXCR3, in mice[2].
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[3]. | [IC 50]
[125I]CXCL10-CXCR3: 1.5 nM (Ki, in CXCR3-CHO cell membranes); [125I]CXCL11-CXCR3: 3.2 nM (Ki, in CXCR3-CHO cell membranes) | [References]
[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 |
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| Company Name: |
SPIRO PHARMA
|
| Tel: |
|
| Website: |
www.spiropharma.com.cn |
| Company Name: |
Musechem
|
| Tel: |
+1-800-259-7612 |
| Website: |
www.musechem.com |
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