NBI-74330

SKU: orb3027292

Description

NBI-74330 is a high-affinity CXCR3 antagonist that inhibits the binding of CXCR3 to its ligands CXCL10 and CXCL11, reduces the formation of atherosclerotic plaques in LDL receptor-deficient mice, and decreases the migration of CD4+ T cells and macrophages to the peritoneum.

Research Area

Cell Biology, Immunology & Inflammation, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 855527-92-3
• MW: 605.58
• Purity: 99.37% (May vary between batches)
• Formula: C₃₂H₂₇F₄N₅O₃
• SMILES: [C@@H](N(CC=1C=CC=NC1)C(CC2=CC(C(F)(F)F)=C(F)C=C2)=O)(C)C=3N(C(=O)C=4C(N3)=NC=CC4)C5=CC=C(OCC)C=C5
• Target: CXCR
• Solubility: DMSO:80 mg/mL (132.1 mM);10% DMSO+90% Corn Oil:3.3 mg/mL (5.45 mM)

Bioactivity

• Target IC50:
  [125I]-CXCL10-CXCR3:1.5 nM (Ki, in CXCR3-CHO cell membranes)|[125I]-CXCL11-CXCR3:3.2 nM (Ki, in CXCR3-CHO cell membranes)
• In Vivo:
  Methods: DBA/1J mice were treated with NBI-74330 (100 mg/kg) in a collagen-induced arthritis (CIA) model. Arthritis scores and histopathological changes were assessed. Flow cytometry was used to investigate the effects of NBI-74330 on Th1 (IFN-γ, TNF-α, T-bet, STAT4, Notch-3, and RANKL), Th17 (IL-21, IL-17A, STAT3, and RORγt), and Th22 (IL-22) cell expression in splenic CD4 and CXCR3 T cells. RT-PCR was used to assess mRNA levels of IFN-γ, TNF-α, T-bet, RANKL, IL-17A, RORγt, and IL-22 in knee joint tissues. ELISA was used to measure serum protein levels of IFN-γ, TNF-α, and IL-17A. Results: The severity of arthritis scores and histological severity of inflammation were significantly reduced in NBI-74330-treated CIA mice. The percentages of CD4IFN-γ, CD4TNF-α, CD4T-bet, CD4STAT4, CD4Notch-3, CXCR3IFN-γ, CXCR3TNF-α, CXCR3T-bet, CXCR3STAT4, CXCR3Notch-3, CD4RANKL, CD4IL-21, CD4IL-17A, CD4STAT3, CD4RORγt, and CD4IL-22 cells were decreased in NBI-74330-treated CIA mice. In addition, NBI-74330 treatment downregulated the mRNA levels of IFN-γ, TNF-α, T-bet, RANKL, STAT3, IL-17A, RORγt, and IL-22.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

NBI74330

Quick Database Links

Gene Symbol

CXCR