Navarixin-SCH-527123-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENavarixinCat. No.: HY-10198CAS No.: 473727-83-2Synonyms: SCH 527123; MK-7123分式: CHNO分量: 397.42作靶点: CXCR作通路: GPCR/G Protein; Immunology/Inflammation储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 D

2、MSO : 50 mg/mL (125.81 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.29 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (6.29 mM); Suspended solution; Need ultrasonic3. 请依序添加每种溶剂： 10% DMSO

3、 90% corn oilSolubility: 2.5 mg/mL (6.29 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Navarixin种有效的 CXCR1 和 CXCR2 的别构拮抗剂，对猕猴 CXCR1 的 Kd 值为 41 nM，对，和猕猴 CXCR2 的 Kd 值分别为 0.20 nM，0.20 nM，0.08 nM。IC50 & Target Cynomolgus CXCR2 Mouse CXCR2 Rat CXCR2 Cynomolgus CXCR10.08 nM (Kd) 0.2 nM (Kd) 0.2 nM (Kd) 41 nM

4、(Kd)体外研究 Navarixin is a potent, allosteric antagonist of both CXCR1 and CXCR2, with Kd values of 41 nM forcynomolgus 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

5、 (3 nM) significantly inhibits the potency and efficacy of CXCL1-induced neutrophils (PMN)chemotaxis. Navarixin (300 nM) significantly decreases chemokine potency and slightly decreases maximalcell movement for Ba/F3-CXCR1 cells 2. Navarixin (25 M) is sufficient to block IL-8-mediated CXCR2activatio

6、n in HCT116, E2, Caco2, and IIIe cells, in which phosphorylation of downstream kinases of CXCR2is reduced in a concentration-dependent manner 3.体内研究 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 follo

7、wing the intranasal lipopolysaccharide (LPS) administration. Inrats, Navarixin (0.1-3 mg/kg p.o.) suppresses the pulmonary neutrophilia (ED=1.8 mg/kg) and increase inbronchoalveolar lavage (BAL) mucin content (ED50=0.1 mg/kg) induced by intratracheal (i.t.) LPS 1.PROTOCOLCell Assay 2 Recombinant cel

8、ls are resuspended at 1106/mL in assay buffer (phenol red free-RPMI 1640 supplementedwith 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 highaffinity. Chemoattr

9、actants (30 L) diluted in assay buffer are dispensed into the bottom wells of disposablemicrochemotaxis 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 L) are applied to each spot on the filter. After incuba

10、tion (90min for BaF/3 cells and 30 min for PMN in a CO2 incubator), the filters are removed. Migrated cells in thebottom wells are transferred to a Microlite luminometer plate, and 25 L of ATPlite one-step are added toeach well. After incubation at room temperature for 10 min, luminescence intensity

11、 is measured using aluminometer 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Male BALB/c mice weighing between 20 and 25 g are anesthetized by intraperitoneal injection of ketamine2/3 Master of Small Molecules 您边的抑制剂师w

12、ww.MedChemE(100 mg/kg) and xylazine (10 mg/kg), and 50 L of a 1 mg/mL LPS solution (50 g/mouse) is instilled into thelungs via the intranasal route of administration. Control mice receive intranasal injection of 50 L of isotonic(0.9%) saline. Navarixin (0.1-10 mg/kg, p.o.) is suspended in 0.4% methy

13、lcellulose and given orally bygavage 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 1Male Sprague-Dawley rats (200 g) are anesthetized with 5% isoflurane supplemente

14、d with oxygen andreceive 100 Lof LPS (100 g/mL), dissolved in isotonic (0.9%) saline to deliver a dose of 10 g/rat. Controlanimals receive 100 L of isotonic saline. Navarixin (0.1-3 mg/kg, p.o.) is suspended in 0.4% methylcellulosevehicle and given orally 2 h before the LPS challenge. Control rats r

15、eceive oral methylcellulose (10 mL/kg).Only one dose of Navarixin or vehicle is given in these experiments 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Nat Microbiol. 2017 May 15;2:17072. J Allergy Clin Immunol. 2016 Jul;138(1):114-122.

16、e4. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Aug 10;1002:42-53. Mol Pain. 2017 Jan-Dec;13:1744806917730212. Patent. US20180235964A1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Gonsiorek W, et al. Pharmacological characterization of Sch527123, a potent allosteric

17、CXCR1/CXCR2 antagonist. J Pharmacol ExpTher. 2007 Aug;322(2):477-85.2. Chapman RW, et al. A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production,and goblet cell hyperplasia in animal models of pulmonary inflammation. J Pharmacol Exp Ther. 2007 Aug;322(2):486-93.3. Ning Y, et al. The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclini