| Cas No.: | 457081-03-7 |
| Chemical Name: | 2-(1,1-Dimethylethyl)-9-fluoro-3,6-dihydro-7H-benz[h]-imidaz[4,5-f]isoquinolin-7-one |
| Synonyms: | Merck 5,Merck5 |
| SMILES: | CC(C)(C)C1=NC2=C(N1)C3=C(C=C(C=C3)F)C4=C2C=CNC4=O |
| Formula: | C18H16FN3O |
| M.Wt: | 309.3 |
| Purity: | >98% |
| Sotrage: | 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO |
| Description: | Pyridone 6 is a pan-JAK inhibitor, which potently inhibits the JAK kinase family, with IC50s of 1 nM for JAK2 and TYK2, 5 nM for JAK3, and 15 nM for JAK1, while displaying significantly weaker affinities (130 nM to >10 mM) for other protein tyrosine kinases. |
| Target: | JAK2:1 nM (IC50) Tyk2:1 nM (IC50) JAK3:5 nM (IC50) Murine JAK1:15 nM (IC50) CDK2:3.3 μM (IC50) cAMP-dependent kinase:7.1 μM (IC50) Csk:2.1 μM (IC50) Hck:7.7 μM (IC50) Fyn T:0.5 μM (IC50) p38:11 μM (IC50) MAPK:1.78 μM (IC50) Mek:0.16 μM (IC50) IκB Kinase 2:0.3 μM (IC50) KDR:1.4 μM (IC50) Flt-1:1.52 μM (IC50) Flt-4:0.69 μM (IC50) FGFR:1.48 μM (IC50) FGFR2:0.94 μM (IC50) Tek:24 μM (IC50) PDGFR:1.49 μM (IC50) PKC(α):1.2 μM (IC50) |
| In Vivo: | Pyridone 6 (P6) delays the onset and reduced the magnitude of skin disease in an AD-like skin-disease model of NC/Nga mice. P6-nano strongly ameliorates atopic dermatitis (AD) in NC/Nga mice, exerting an effect comparable to that of betamethasone ointment, a commonly used drug, which also tested as a positive control. In contrast, empty polylactic acid with glycolic acid (PLGA) nanoparticles (C-nano) seemed to have no effect[2]. |
| In Vitro: | Pyridone 6 is tested as an inhibitor of 21 other protein kinases; Pyridone 6 inhibits these kinases with IC50s ranging from 130 nM to >10 μM. Pyridone 6 inhibits IL2 driven proliferation of CTLL cells with IC50=0.1 μM and IL4 driven proliferation with IC50=0.052 μM[1]. Pyridone 6 (P6) is shown to inhibit kinase by interacting within the ATP-binding cleft of each JAK. The IC50 of Pyridone 6 is 3 nM for all of these cytokines; this is comparable to the reported IC50s of Pyridone 6 for JAK2, Tyk2, and JAK3. Pyridone 6 strongly inhibits Th2 and modestly inhibits Th1, whereas it enhances Th17 development when present within a certain range of concentrations. Pyridone 6 reduces IFN-γ 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 naive T cells when present within a certain range of concentrations[2]. |
| Cell Assay: | Naive CD4+ T cells are treated with various concentrations of Pyridone 6 (10 and 30 nM) in RPMI 1640 medium 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]. |
| Animal Administration: | Mice[2] NC/Nga mice are used at the age of 10-15 wk. To assess the effect of Pyridone 6 treatment on AD symptoms, 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 Dfb ointment application; this treatment is repeated twice a week. To assess the effects of recombinant murine IL-17 and IL-22, these cytokines (50 μg/kg) or 100 μL PBS is administered for the same duration as the nanoparticles. Twenty milligrams of 0.064% betamethasone ointment are applied to the dorsal lesion of mice once a week[2]. |
| References: | [1]. Thompson JE, et al. Photochemical preparation of a pyridone containing tetracycle: a Jak protein kinase inhibitor. Bioorg Med Chem Lett. 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 and enhancement of Th17. J Immunol. 2011 Nov 1;187(9):4611-20. |
MSDS
COA
| LOT NO. | DOWNLOAD |
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| 2018-0101 |
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| 2018-0101 |
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