473727-83-2
473727-83-2 structure
- Name: SCH 527123
- Chemical Name: 2-hydroxy-N,N-dimethyl-3-[[2-[[(1R)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzamide
- CAS Number: 473727-83-2
- Molecular Formula: C21H23N3O5
- Molecular Weight: 397.42400
- Catalog: Signaling Pathways GPCR/G Protein CXCR
- Create Date: 2016-03-12 06:57:35
- Modify Date: 2024-01-12 17:19:06
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Navarixin is a potent, allosteric antagonist of both CXCR1 and CXCR2, with Kd values of 41 nM for cynomolgus CXCR1 and 0.20 nM, 0.20 nM, 0.08 nM for mouse, rat and cynomolgus monkey CXCR2, respectivelly.
| Name | 2-hydroxy-N,N-dimethyl-3-[[2-[[(1R)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzamide |
|---|---|
| Synonyms |
(R)-2-Hydroxy-N,N-dimethyl-3-((2-((1-(5-methylfuran-2-yl)propyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)benzamide
Navarixin SCH 527123 |
| Description | Navarixin is a potent, allosteric antagonist of both CXCR1 and CXCR2, with Kd values of 41 nM for cynomolgus CXCR1 and 0.20 nM, 0.20 nM, 0.08 nM for mouse, rat and cynomolgus monkey CXCR2, respectivelly. |
|---|---|
| Related Catalog | |
| Target |
Cynomolgus CXCR2:0.08 nM (Kd) Mouse CXCR2:0.2 nM (Kd) Rat CXCR2:0.2 nM (Kd) Cynomolgus CXCR1:41 nM (Kd) |
| In Vitro | Navarixin is a potent, allosteric antagonist of both CXCR1 and CXCR2, with Kd values of 41 nM for cynomolgus CXCR1 and 0.20 nM, 0.20 nM, 0.08 nM for mouse, rat and cynomolgus monkey CXCR2, respectivelly[1]. Navarixin (1 nM) reduces CXCL8 potency in stimulating Ba/F3-hCXCR2 chemotaxis. Navarixin (3 nM) significantly inhibits the potency and efficacy of CXCL1-induced neutrophils (PMN) chemotaxis. Navarixin (300 nM) significantly decreases chemokine potency and slightly decreases maximal cell movement for Ba/F3-CXCR1 cells[2]. Navarixin (25 μM) is sufficient to block IL-8-mediated CXCR2 activation in HCT116, E2, Caco2, and IIIe cells, in which phosphorylation of downstream kinases of CXCR2 is reduced in a concentration-dependent manner[3]. |
| In Vivo | Navarixin (0.1-10 mg/kg, p.o.) blocks pulmonary neutrophilia (ED50=1.2 mg/kg) and goblet cell hyperplasia (32-38% inhibition at 1-3 mg/kg) in mice following the intranasal lipopolysaccharide (LPS) administration. In rats, Navarixin (0.1-3 mg/kg p.o.) suppresses the pulmonary neutrophilia (ED=1.8 mg/kg) and increase in bronchoalveolar lavage (BAL) mucin content (ED50=0.1 mg/kg) induced by intratracheal (i.t.) LPS[1]. |
| Cell Assay | Recombinant cells are resuspended at 1×106/mL in assay buffer (phenol red free-RPMI 1640 supplemented with 2% FBS). Human neutrophils are resuspended at 2 × 106/mL in the same assay buffer containing 5% FBS. CXCL1 binds only CXCR2 with high affinity, whereas CXCL8 binds both CXCR1 and CXCR2 with high affinity. Chemoattractants (30 μL) diluted in assay buffer are dispensed into the bottom wells of disposable microchemotaxis plates, which are then covered with filter. Cells are preincubated with Navarixin (1-300 nM) in a CO2 incubator for 90 min. Cell aliquots (25 μL) are applied to each spot on the filter. After incubation (90 min for BaF/3 cells and 30 min for PMN in a CO2 incubator), the filters are removed. Migrated cells in the bottom wells are transferred to a Microlite luminometer plate, and 25 μL of ATPlite one-step are added to each well. After incubation at room temperature for 10 min, luminescence intensity is measured using a luminometer[2]. |
| Animal Admin | Mice[1] Male BALB/c mice weighing between 20 and 25 g are anesthetized by intraperitoneal injection of ketamine (100 mg/kg) and xylazine (10 mg/kg), and 50 μL of a 1 mg/mL LPS solution (50 μg/mouse) is instilled into the lungs via the intranasal route of administration. Control mice receive intranasal injection of 50 μL of isotonic (0.9%) saline. Navarixin (0.1-10 mg/kg, p.o.) is suspended in 0.4% methylcellulose and given orally by gavage 2 h before and 4 h after each intranasal administration of LPS. Control animals receive 0.4% methylcellulose (10 mL/kg). In total, four doses of Navarixin or vehicle are given[1]. Rats[1] Male Sprague-Dawley rats (200 g) are anesthetized with 5% isoflurane supplemented with oxygen and receive 100 μLof LPS (100 μg/mL), dissolved in isotonic (0.9%) saline to deliver a dose of 10 μg/rat. Control animals receive 100 μL of isotonic saline. Navarixin (0.1-3 mg/kg, p.o.) is suspended in 0.4% methylcellulose vehicle and given orally 2 h before the LPS challenge. Control rats receive oral methylcellulose (10 mL/kg). Only one dose of Navarixin or vehicle is given in these experiments[1]. |
| References |
| Molecular Formula | C21H23N3O5 |
|---|---|
| Molecular Weight | 397.42400 |
| Exact Mass | 397.16400 |
| PSA | 111.88000 |
| LogP | 2.97550 |
| Storage condition | 2-8℃ |