| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 1mg | 电议 |
| 2mg | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
Preparation Method | Assay for Jak family protein kinase activity. Jak3, Tyk2, Jakl and Jak2 kinase domains with N-terminal 'Flag' affinity tags were expressed in Sf9 cells using standard baculovirus methods and purified by antiFlag aflinity chromatography, followed by gel filtration chromatography. Jak family tyrosine kinase activity was measured by detection of the tyrosine phosphorylated peptide amino hexanoyl biotin-EQEDEPEGDYFEWLE-NH2 (S, hereafter) detected by homogenous time resolved fluorescence (HTRF) using a europium labeled antibody to phosphotyrosine (pY20). For determining the mode of inhibition of Pyridone 6 with respect to peptide substrate, y33P ATP was included in the assays and incorporated radioactivity was measured using SAM2.Assay methods for PKA, PKCa and cdk2. Cyclin E-Cyclin dependent kinase 2 (cdk2) complex was assayed by SPA using the biotinylated peptide PKTPKKAKKL. Bovine PKA catalytic subunit was assayed by SPA using the biotinylated peptide LRRASLG as a substrate.PKCa was assayed by SPA using the biotinylated peptide AAKIQASFRGHMARKK. |
Applications | Pyridone 6 inhibited Tyk2, Jak1, Jak2, Jak3 with IC50s of 1nM,15nM,1nM and 5nM, respectively. |
Cell lines | WIF-B cells |
Preparation Method | Incubated cells with the pan-JAK inhibitor pyridone 6 (P6, 1 uM) for two hours prior to OSM-Dex addition and assayed channel activity four days later. |
Reaction Conditions | 1 uM for two hours |
Applications | P6 did not significantly affect TRPM7 current on its own, but blocked the current depression in response to OSM-Dex. |
Animal models | NC/Nga mice |
Preparation Method | Nanoparticles containing Pyridone 6 (2 mg/body) or empty nanoparticles as a negative control (C-nano) were dissolved in 0.1 ml saline and administered s.c. 1 d after Dfb ointment application; this treatment was repeated twice a week. |
Dosage form | Pyridone 6 (2 mg/body) s.c. |
Applications | Pyridone 6-nano strongly ameliorated AD in NC/Nga mice, exerting an effect comparable to that of betamethasone ointment, a commonly used drug. |
| 产品描述 | Pyridone 6 inhibits Jak3 with K(I)=5 nM; Pyridone 6 also inhibits Jak family members Tyk2 and Jak2 with IC(50)=1 nM and Jak1 with IC(50)=15 nM. Pyridone 6 was tested as an inhibitor of 21 other protein kinases; it inhibited these kinases with IC(50)s ranging from 130 nM to 10 μM[1]. Pyridone 6 strongly inhibited Th2 and modestly inhibited Th1, whereas it enhanced Th17 development when present within a certain range of concentrations. This is mostly due to strong suppression of the IFN-γ/STAT1, IL-2/STAT5, and IL-4/STAT6 signaling pathways by Pyridone 6, which all inhibit Th17 differentiation, as well as modest suppression of IL-6/STAT3, which is essential for Th17 differentiation[2，5]. In mice, Mean outward current decreased by 44% in WIF-B hepatoma cells incubated with the established hepatic differentiating factors oncostatin M/dexamethasone for 1-8 days. Pre-incubation with pyridone 6, a pan-JAK inhibitor, blocked the current reduction[3]. Pyridone 6 blocks IL2 and IL4 dependent proliferation of CTLL cells and inhibits the phosphorylation of STAT5 as measured by Western blotting[1]. Pyridone 6 is a more sensitive and specific inhibitor of JAK-STAT3 activity compared with AG490 and potently inhibited the growth of primary myeloma cells and myeloma-derived cell lines grown on BMSCs[4]. Inhibition of JAK by pyridone 6 resulted in the suppression of STAT3 phosphorylation and secretion of a subset of chemokines and JAK-activating cytokines[6]. Cytomix-induced STAT1 activation was lower and CXCR3 ligand mRNA production was more sensitive to Pyridone 6 and AG-490 in asthmatic than nonasthmatic ASMCs, but CXCL10/CXCL11 release was inhibited by the same proportion[7]. References: |
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