RS-504393 _CCR2 Antagonist - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERS 504393Cat. No.: HY-15418CAS No.: 300816-15-3分式: CHNO分量: 417.5作靶点: CCR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 DMSO : 12.5 mg/mL (29.94 mM; Nee

2、d ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 1.25 mg/mL (2.99 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 1.25 mg/mL (2.99 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 RS 504393种选择性的 CCR2 拮抗剂，作于重 组 CCR2 和 CCR1 受体，

3、IC50 值分别为 89 nM 和 100M。IC50 & Target CCR2 Human 1a receptor Human 1d receptor 5HT-1a receptor89 nM (IC50) 72 nM (IC50) 460 nM (IC50) 1070 nM (IC50)体外研究 RS 504393 inhibits the MCP-1-induced chemotaxis with an IC50 of 330 nM. RS 504393 treatmentsuppresses allergen induced -hexosaminidase release signi

4、ficantly. Without allergen priming, MCP-1induces mast cell degranulation, which is completely suppressed by RS 504393 4.体内研究 RS504393 (0.3-3 g) with CCL2 progressively blocks thermal hyperalgesia dose-dependently in mice 1. RS504393 (5 mg/kg, i.v.) supresses the elevated numbers of leukocytes and in

5、creased total protein content inBALF induced by The LPS. RS504393 significantly down regulates the LPS-induced elevation of IL-1, PAI-1mRNA and protein expressions. RS504393 significantly suppresses induced lung edema, protein-rich fluid,polymorphonuclear accumulation and bronchial wall thickening i

6、nduced by LPS 2. RS-504393 significantlyreduces renal pathology, especially the extensive interstitial fibrosis mediated by decrease in type I collagensynthesis in a UUO model 3.PROTOCOLKinase Assay 4 Isolated mast cells are sensitized by incubation with anti-DNP IgE in RPMI1640 containing 10 ng/mL

7、ofmurine recombinant IL-3, 10 ng/mL of recombinant SCF, and 5% murine serum. The cells are then washedwith HBSS containing 10 ng/mL of murine recombinant IL-3, 10 ng/mL of recombinant SCF, 0.04% BSA, and10 mM HEPES. Resuspended cells at a concentration of 2 to 8104 cells/100 L are transferred intotr

8、iplicate wells of a 96 well U-bottom plate and allowed to equilibrate at 37C for 10 minutes before theaddition of DNP-albumin or compound 48/80. After 45 minutes, the plate is centrifuged at 290 g for 5 minutesat 4C. The -hexosaminidase activity of the culture supernatant is determined using a Publi

9、shed protocol.Fifty-L aliquots of the supernatant are placed in wells of another 96-well plate together with 100 L of 2.5mM p-nitrophenyl-N-acetyl -d glucosaminide solubilized in 0.04mol/Lcitrate buffer adjusted to pH 4.5 withdisodium phosphate. After incubation at 37C for 90 minutes, the reactions

10、are terminated by addition of 50 L of 0.4mol/Lglycin adjusted to pH 10.7 with sodium hydroxide. The colored product is measured at 405 nmwith a reference filter of 570 nm. The relative release of -hexosaminidase is defined as the activity in thesupernatant of the tested cells divided by the activity

11、 in the positive control cell supernatant, multiplied by100. Compound 48/80 stimulus is used for assay control.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male C57BL/6J mice (n=30) and male homozygote CCR1, CCR2 and CCR3 knockout mice (n=12,

12、in eachAdministration 2 phenotype), 6-8 weeks old and weighing 202 g, are anesthetized with a mixture of ketamine (80 mg/kg) andxylazine (30 mg/kg) given intraperitoneally. Intranasal administration of PBS or LPS (5 mg/kg) is performed ina volume of 1 mL/kg body weight. C57BL/6J mice are treated wit

13、h vehicle or RS504393 (5 mg/kg)intraperitoneally 30 min before LPS challenge. Four hours after LPS challenge, mice are terminated by anintraperitoneal injection of an overdose of pentobarbitone. The mice are kept on a 12-h light/dark cycle with2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEaccess

14、to mice chow and water ad libitum.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 Cytokine. 2018 Oct;110:70-77. Mol Immunol. 2019 May;109:140-148. Neurosci Lett. 2019 May 14;701:100-105.See more customer validations on HYPERLINK / www.MedChe

15、mEREFERENCES1. Baamonde, Ana., et al. Involvement of glutamate NMDA and AMPA receptors, glial cells and IL-1 in the spinal hyperalgesia evoked bythe chemokine CCL2 in mice. Neuroscience Letters (2011), 502(3), 178-181.2. Yang, Dong., et al. Roles of CC chemokine receptors (CCRs) on lipopolysaccharid

16、e-induced acute lung injury. Respiratory Physiology &Neurobiology (2010), 170(3), 253-259.3. Kitagawa, Kiyoki., et al. Blockade of CCR2 ameliorates progressive fibrosis in kidney. American Journal of Pathology (2004), 165(1),237-246.4. Tominaga T, et al. Blocking mast cell-mediated type I hypersensi

17、tivity in experimental allergic conjunctivitis by monocytechemoattractant protein-1/CCR2. Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5181-8.5. Mirzadegan T, et al. Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a commonchemokine receptor motif within the h