R406 - Syk 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemER406Cat. No.: HY-12067CAS No.: 841290-81-1分式: CHFNOS分量: 628.63作靶点: Syk作通路: Protein Tyrosine Kinase/RTK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 : 61 mg/mL (97.04 mM)H2O : 40% PEG300 5%

2、Tween-80 45% salineSolubility: 2.5 mg/mL (3.98 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (3.98 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 R406种ATP竞争性的 Syk 抑制剂，Ki 为 30 nM，有效抑制 Syk 激酶活性

3、，IC50 为 41 nM。IC50 & Target Ki: 30 nM (Syk) 1IC50: 41 nM (Syk) 1体外研究 R406 also exhibits antagonistic activity for adenosine A3 receptor with an IC50 estimated to be 93 nM 1. InRamos B lymphoma cells, B-cell receptor (BCR) crosslinking induces robust phosphorylation of B-cell linkerprotein (BLNK), wh

4、ich is ablated by addition of the Syk inhibitor R406. Additionally, R406 significantlyreduces constitutive Syk signaling in EBV+ cell lines derived from patients with Post-transplantlymphoproliferative disorder (PTLD), termed SLCL. Therefore, R406 inhibits Syk activation 2.体内研究 Prophylactic treatmen

5、t of mice with R406 administers 1 h before immune complex challenge reduces thecutaneous reverse passive Arthus reaction by approximately 72 and 86% at 1 and 5 mg/kg, respectively,compared with the vehicle control. The net optical density reading of extravasated dye extracted aftertreatment with R40

6、6 at 1 or 5 mg/kg R406 is reduced from 0.14 (vehicle) to 0.04 or 0.02, respectively (p 1.PROTOCOLKinase Assay 1 The fluorescence polarization reactions are performed. For Kidetermination, duplicate 200 L reactions areset up at eight different ATP concentrations from 200 M (2-fold serial dilutions) i

7、n the presence of eitherDMSO or R406 at 125, 62.5, 31.25, 15.5, or 7.8 nM. At different time points, 20 L of each reaction isremoved and quenched to stop the reaction. For each concentration of R406, the rate of reaction at eachconcentration of ATP is determined and plotted against the ATP concentra

8、tion to determine the apparent Kmand Vmax (maximal rate). Finally the apparent Km (or apparent Km/Vmax) is plotted against the inhibitorconcentration to determine the Ki. All data analysis is performed using Prism and Prism enzyme kineticsprograms 1MCE has not independently confirmed the accuracy of

9、 these methods. They are for reference only.Cell Assay 2 Cells (0.5-1106 cells/mL) are plated in serial dilutions of small molecule inhibitors R406, LY294002, orPD98059 (0-10 M), or equivalent amounts of vehicle (DMSO, 0-1:1000). Drug and media are replenishedafter 48 h of a total of 96 h in culture

10、 at 37C. Cell cycle analysis using propidium iodide. The percentage ofapoptotic cells is determined using Annexin V-enhanced GFP (EGFP) apoptosis detection kits. Data isanalyzed on a FACScan flow cytometer 2.MCE has not independently confirmed the accuracy of these methods. They are for reference on

11、ly.Animal Mice 1Administration 1 Mice are challenged intravenously with 1% ovalbumin (OVA) in saline (10 mg/kg) containing 1% Evans bluedye. Ten minutes later, mice are anesthetized with isofluorane and shaved dorsolaterally. The rabbit anti-OVA IgG (50 g/25 L) is injected intradermally on the left

12、side of the back at three adjacent locations. Threeinjections of rabbit polyclonal IgG (50 g/25 L) on the opposite side of the same animal served as controls.R406 (1 and 5 mg/kg) or vehicle (67% PEG 400) is administered to animals 60 min before antibody/antigen2/3 Master of Small Molecules 您边的抑制剂师ww

13、w.MedChemEchallenge. Four hours after challenge, the animals are euthanized, and skin tissue is assessed for edemaand inflammation by measuring dye extravasation into the surrounding tissue. Punch biopsy of the injectionsites (8 mm) are incubated in 2 mL of formamide at 80C overnight. The concentrat

14、ion of the extravasatedEvans blue dye is measured spectrophotometrically at OD610.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 Cell. 2018 Oct 4;175(2):442-457.e23. Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Arthritis Rheumatol. 2

15、018 Sep;70(9):1419-1428. J Biol Chem. 2018 Apr 27;293(17):6410-6433. J Pharmacol Sci. 2017 May;134(1):29-36.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Braselmann S, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces i

16、mmunecomplex-mediated inflammation. J Pharmacol Exp Ther, 2006, 319(3), 998-1008.2. Hatton O, et al. Syk-induced phosphatidylinositol-3-kinase activation in Epstein-Barr virus posttransplant lymphoproliferative disorder.Am J Transplant. 2013 Apr;13(4):883-90.3. Kitai M, et al. Effects of a spleen tyrosine kinase inhibitor on progression of the lupus nephritis in