Pyridone-6-CMP-6-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPyridone 6Cat. No.: HY-14435CAS No.: 457081-03-7Synonyms: CMP 6; JAK Inhibitor分式: CHFNO分量: 309.34作靶点: JAK作通路: Epigenetics; JAK/STAT Signaling; Stem Cell/Wnt储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解

2、性数据体外实验 DMSO : 100 mg/mL (323.27 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (8.08 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 (8.08 mM); Suspended solution; Need ultrasonic3. 请依序添加每种溶剂

3、： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (8.08 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Pyridone 6种 pan-JAK 抑制剂，有效抑制 JAK 激酶家族，作于 JAK2，TYK2，JAK3 和 JAK1，IC50 分别为 1 nM，1 nM，5 nM 和 15 nM。IC50 & Target JAK2 Tyk2 JAK3 Murine JAK11 nM (IC50) 1 nM (IC50) 5 nM (IC50) 15 nM (IC50)CDK2 cAMP-dependent Csk

4、Hck3.3 M (IC50) kinase 2.1 M (IC50) 7.7 M (IC50)7.1 M (IC50)Fyn T p38 MAPK Mek0.5 M (IC50) 11 M (IC50) 1.78 M (IC50) 0.16 M (IC50)IB Kinase 2 KDR Flt-1 Flt-40.3 M (IC50) 1.4 M (IC50) 1.52 M (IC50) 0.69 M (IC50)FGFR FGFR2 Tek PDGFR1.48 M (IC50) 0.94 M (IC50) 24 M (IC50) 1.49 M (IC50)PKC()1.2 M (IC50)

5、体外研究 Pyridone 6 is tested as an inhibitor of 21 other protein kinases; Pyridone 6 inhibits these kinases with IC50sranging from 130 nM to 10 M. Pyridone 6 inhibits IL2 driven proliferation of CTLL cells with IC50=0.1 Mand IL4 driven proliferation with IC50=0.052 M 1. Pyridone 6 (P6) is shown to inhi

6、bit kinase by interactingwithin the ATP-binding cleft of each JAK. The IC50 of Pyridone 6 is 3 nM for all of these cytokines; this iscomparable to the reported IC50s of Pyridone 6 for JAK2, Tyk2, and JAK3. Pyridone 6 strongly inhibits Th2and modestly inhibits Th1, whereas it enhances Th17 developmen

7、t when present within a certain range ofconcentrations. Pyridone 6 reduces IFN- and IL-13, whereas it enhances IL-17 and IL-22 expression.Pyridone 6 also inhibits both Th1 and Th2 development, whereas it promotes Th17 differentiation from naiveT cells when present within a certain range of concentra

8、tions 2.体内研究 Pyridone 6 (P6) delays the onset and reduced the magnitude of skin disease in an AD-like skin-diseasemodel of NC/Nga mice. P6-nano strongly ameliorates atopic dermatitis (AD) in NC/Nga mice, exerting aneffect comparable to that of betamethasone ointment, a commonly used drug, which also

9、 tested as a positivecontrol. In contrast, empty polylactic acid with glycolic acid (PLGA) nanoparticles (C-nano) seemed to haveno effect 2.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEPROTOCOLCell Assay 2 Naive CD4+ T cells are treated with various concentrations of Pyridone 6 (10 and 30 nM) in

10、 RPMI 1640medium 1 h before the appropriate cytokines are added to create each Th-differentiating condition.Immunoblotting is performed using antiphospho-STAT protein Abs or anti-total STAT protein Abs 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.A

11、nimal Mice 2Administration 2 NC/Nga mice are used at the age of 10-15 wk. To assess the effect of Pyridone 6 treatment on ADsymptoms, nanoparticles containing Pyridone 6 (2 mg/body) or empty nanoparticles as a negative control (C-nano) are dissolved in 0.1 mL saline and administered s.c. 1 d after D

12、fb ointment application; this treatmentis repeated twice a week. To assess the effects of recombinant murine IL-17 and IL-22, these cytokines (50 g/kg) or 100 L PBS is administered for the same duration as the nanoparticles. Twenty milligrams of 0.064%betamethasone ointment are applied to the dorsal

13、 lesion of mice once a week 2.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 Leukemia. 2012 Oct;26(10):2233-44. Patent. US20160368910A1. Patent. US20140309249A1. Chem Biol. 2012 Jan 27;19(1):140-54.See more customer validations on HYPERLINK

14、 / www.MedChemEREFERENCES1. Thompson JE, et al. Photochemical preparation of a pyridone containing tetracycle: a Jak protein kinase inhibitor. Bioorg Med ChemLett. 2002 Apr 22;12(8):1219-23.2. Nakagawa R, et al. Pyridone 6, a pan-JAK inhibitor, ameliorates allergic skin inflammation of NC/Nga mice via suppression of Th2 andenhancement of Th17. J Immunol. 2011 Nov 1;187