HTS01037 - FABP Antagonist - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEHTS01037Cat. No.: HY-101503CAS No.: 682741-29-3分式: CHNOS分量: 337.37作靶點(diǎn): FABP作通路: Metabolic Enzyme/Protease儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 150 mg/mL (444.62 mM)H2O : 40% PEG30

2、0 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.41 mM); Suspended solution; Need ultrasonic2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.41 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubil

3、ity: 2.5 mg/mL (7.41 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 HTS01037結(jié)合脂 酸的抑制劑。它也 由AFABP / aP2介導(dǎo)的蛋質(zhì)-蛋質(zhì)相互作的拮抗劑，Ki值為0.67M。IC50 & Target IC50: 0.67 M (AFABP/aP2) 1體外研究 HTS01037 functions as a high affinity ligand of AFABP/aP2 with an apparent Ki of 0.67 M. HTS01037 issomewhat selective for AFABP/aP2,

4、 but at higher concentrations is a pan-specific FABP inhibitor. HTS01037inhibits lipolysis in 3T3-L1 adipocytes and reduces LPS-stimulated inflammation in cultured macrophages.HTS01037 acts as an antagonist of the protein-protein interaction between AFABP/aP2 and hormonesensitive lipase but does not

5、 activate PPAR in macrophage or CV-1 cells 1. Treatment of microglial cellswith HTS01037 increases expression of Ucp2 and arginase in the presence or absence of palmitic acid.Moreover, cells exposed to HTS01037 exhibits attenuated expression of inducible nitric oxide synthase(iNOS) compared to palmi

6、tic acid alone indicating reduced NFB signaling 2. Treatment of macrophageswith HTS01037results in a marked decrease in both basal and fatty acid-stimulated LTC4 secretion but nochange in 5-HETE production or 5-lipoxygenase expression 3.PROTOCOLKinase Assay 1 To analyze the ligand (HTS01037) binding

7、 properties of the FABPs, the fluorescent ligand 1-anilinonapthalene 8-sulfonic acid (1,8-ANS) is utilized. 1,8 ANS is dissolved in absolute ethanol and dilutedwith 25 mM Tris-HCl (pH 7.4) to a final concentration of 5 M (final EtOH concentration of 0.05%). Protein istitrated into 500 L 1,8-ANS and

8、the fluorescence enhancement is measured using a Perkin Elmer 650-10Sfluorescence spectrophotometer with 4 nm excitation and emission slit widths. Quantitative analysis of ligandbinding is evaluated using non-linear regression using PRISM software 1.MCE has not independently confirmed the accuracy o

9、f these methods. They are for reference only.Cell Assay 2 Cells are pretreated with HTS01037 or vehicle for 3 h and then challenged with or without palmitic acid for 1h. Cells are then exposed to the ROS Deep Red Dye for 1 h in 5% CO2 at 37C. Intracellular superoxide andhydroxyl radicals react with

10、the deep red dye, producing a fluorescent signal which is measured using aspectrophotometer at 650Ex/675Em 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Hertzel AV, et al. Identification and characterization of a small molecule inhibito

11、r of Fatty Acid binding proteins. J Med Chem. 2009 Oct8;52(19):6024-31.2. Duffy CM, et al. Identification of a fatty acid binding protein4-UCP2 axis regulating microglial mediated neuroinflammation. Mol Cell2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemENeurosci. 2017 Apr;80:52-57.3. Long EK, et al. Fatty acids induce leukotriene C4 synthesis in macrophages in a fatty acid binding protein-dependent manner. BiochimBiophys Acta. 2013 Jul;1831(7):1199-207.McePdfHeightCaution: Product