IQ-1S-free-acid _JNK 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEIQ-1S free acidCat. No.: HY-100233CAS No.: 23146-22-7分式: CHNO分量: 247.25作靶點(diǎn): JNK作通路: MAPK/ERK Pathway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 : 32 mg/mL (129.42 mM)H2O : 40% PEG300 5% T

2、ween-80 45% salineSolubility: 1.67 mg/mL (6.75 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.67 mg/mL (6.75 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 oilSolubility: 1.67 mg/mL (6.75 mM)

3、; Clear solutionBIOLOGICAL ACTIVITY物活性 IQ-1S free acid種 NF-B/激活蛋1 (AP-1) 抑制劑，IC50 為 2.30.41 M。IQ-1S free acid 對(duì)三種 JNK都具有的結(jié)合親和 (Kd 值)，對(duì) JNK3，JNK1 和 JNK2 的 Kd 值分別為 100 nM，240 nM 和 360 nM。IC50 & Target JNK3 JNK1 JNK2 CK1100 nM (Kd) 240 nM (Kd) 360 nM (Kd) 0.38 M (Kd)PI3K MKNK20.47 M (Kd) 0.92 M (Kd)體外研

4、究 Compound IQ-1S is a potent, noncytotoxic inhibitor of pro-inflammatory cytokine interleukin (IL)-1, IL-1, IL-6, IL-10, tumor necrosis factor (TNF)-, interferon-, and granulocyte-macrophage colony-stimulating factorand nitric oxide production by human and murine monocyte/macrophages. The effect of

5、IQ-1S is evaluatedon LPS-induced cytokine production in human PBMCs. Among the 12 cytokines analyzed, LPS (200 ng/mL)consistently induces five (IL-1, IL-1, IL-6, IL-10, and TNF-) in PBMCs compared with DMSO-treatedcontrol cells. Production of all of these cytokines is significantly inhibited by 20 M

6、 IQ-1S. Among them, TNF- production is inhibited completely by IQ-1 (99%), the levels of IL-1, IL-1, and IL-10 are decreased by85%, and IL-6 production is decreased by 33% 1.體內(nèi)研究 When mice are dosed with 12.5 and 30 mg/kg IQ-1S (The sodium salt of IQ-1S) i.p., the serum exposure ofthe compound is al

7、so good, with AUC0-12h values of 2.9 and 7.4 M/h, respectively 1.PROTOCOLCell Assay 1 Human PBMCs are plated in 96-well plates at a density of 2105 cells/well in culture medium supplementedwith 3% (v/v) endotoxin-free FBS. PBMCs are pretreated with 20 M IQ-1S or DMSO for 30 min, followed byaddition

8、of 200 ng/ml LPS for 24 h. A human cytokine MultiAnalyte ELISArray Kit is used to evaluate variouscytokines (IL-1, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, interferon (IFN)-, TNF-, and granulocyte-macrophage colony-stimulating factor in supernatants of PBMCs 1.MCE has not independently co

9、nfirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 For in vivo analysis, 12.5 or 30 mg/kg i.p. doses of IQ-1S (The sodium salt of IQ-1) are administered toBALB/c mice (15-20 animals/group), and the mice are sacrificed at various time points after compoun

10、dadministration. For quantification, a calibration curve is established using mouse serum samples spiked withknown concentrations of IQ-1S (0.1-20 M), and a linear dependence of the peak area with IQ-1Sconcentration is obtained (correlation coefficient r=0.997). The area under the serum concentratio

11、n-timecurve (AUC0-12h) is calculated using the linear trapezoidal method up to the last measured concentration2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Schepetkin IA, et al. Identification and characterization of a novel class of c-Jun N-terminal kinase inhibitors. Mol Pharmacol. 2012Jun;81(6):832-45.McePdfHeightCaution: Product ha