PF-06651600 - JAK 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPF-06651600Cat. No.: HY-100754CAS No.: 1792180-81-4分式: CHNO分量: 285.34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溶解性数据体外实验 DMSO : 150 mg/mL (52

2、5.69 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 3.5046 mL 17.5230 mL 35.0459 mL5 mM 0.7009 mL 3.5046 mL 7.0092 mL10 mM 0.3505 mL 1.7523 mL 3.5046 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作

3、液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (8.76 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (8.76 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂

4、师www.MedChemE物活性 PF-06651600种强效的 JAK3 选择性抑制剂, 其 IC50 值为 33.1 nM。IC50 & Target JAK333.1 nM (IC50)体外研究 PF-06651600 is a potent JAK3-selective inhibitor which can inhibit the JAK3 kinase activity with an IC50 of33.1 nM but without activity (IC5010000 nM) against JAK1, JAK2, and TYK2. PF-06651600 inhibi

5、ts thephosphorylation of STAT5 elicited by IL-2, IL-4, IL-7, and IL-15 with IC50 values of 244, 340, 407, and 266nM, respectively. PF-06651600 also inhibits the phosphorylation of STAT3 elicited by IL-21 with an IC50 of355 nM. Functional assessment in T-cell differentiation assays demonstrate that P

6、F-06651600 suppressesTh1 and Th17 differentiation as measured by IFN, after 5 days under Th1 conditions, and IL-17 production,after 6 days under Th17 conditions, with IC50 values of 30 nM and 167 nM, respectively. PF-06651600 alsosuppresses Th1 and Th17 function as measured by the inhibition of IFN

7、production (IC50=48 nM) and IL-17production (IC50=269 nM) in cells that have been previously differentiated and rested before being treatedwith PF-06651600 1.体内研究 In the rat adjuvant-induced arthritis (AIA) model, PF-06651600 reduces paw swelling with an unbound EC50of 169 nM. Similarly, PF-06651600

8、 significantly reduces disease severity in the experimental autoimmuneencephalomyelitis (EAE) mouse model when dosed either therapeutically at 30 or 100 mg/kg orprophylactically at 20 and 60 mg/kg. The efficacy of PF-06651600 in these two rodent models ofinflammatory and autoimmune diseases illustra

9、tes that JAK3-selective inhibition can be sufficient to havedisease modifying effects in human diseases 1.PROTOCOLCell Assay 1 To study the effect of PF-06651600 on Th17 cells post differentiation, skewed Th17 cells are washed, restedwith medium for overnight and resuspended in medium containing the

10、 same concentrations of cytokines asduring skewing but without anti-CD3 or anti-CD28 antibodies, in the presence of PF-06651600 at 10 differentconcentrations for 2 additional days. On Day 9, supernatant is harvested from each well and IL-17A isdetermined 1.MCE has not independently confirmed the acc

11、uracy of these methods. They are for reference only.Animal The effect of JAK3 inhibition by PF-06651600 is evaluated in vivo using a therapeutic dosing paradigm in aAdministration 1 rat adjuvant-induced arthritis. When individual hind paw volume measurements indicate an increase of 0.2mL (or greater

12、) in a single hind paw, animals are randomly assigned to a treatment group. Daily treatmentwith PF-06651600 is administered via oral gavage. Treatment groups for Experiment 1 are: 80, 15, or 6mg/kg of PF-06651600 or vehicle (2% Tween 80/0.5% methylcellulose/deionized water). Treatment groupsfor Expe

13、riment 2 are: 30, 10, and 3 mg/kg of PF-06651600 or vehicle (0.5% methylcellulose/de-ionizedwater/1 mEQ hydrochloric acid). Treatment groups for Experiment 3 are: 10, 1, 0.3 and 0.1 mg/kg of PF-06651600 or vehicle (0.5% methylcellulose/de-ionized water/1 mEQ hydrochloric acid). Treatment continuesfo

14、r 7 days 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE1. Telliez JB, et al. Discovery of a JAK3-Selective Inhibitor: Functional Differentiation of JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition. ACS Chem Biol. 2016 Dec 16;11(12