生物活性

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.

体外研究

Pyridone 6 was tested as an inhibitor of 21 other protein kinases; Pyridone 6 inhibited these kin with IC50s ranging from 130 nM to >10 μM. Pyridone 6 inhibited IL2-driven CTLL cell proliferation,50=0.1 μM and IL4-driven proliferation, IC50=0.052 μM[1]. Pyridone 6 (P) was shown to inhibit the kinases by interacting within the ATP-binding cleft of each JAK. The IC50 of Pyridone 6 for all of thesetokines was 3 nM; this is quite comparable to the reported IC50 of Pyridone 6 for JAK2, Tyk2 and JAK3 Pyridone 6 potently inhibited Th2 and moderately inhibited Th1, while it enhanced the development of Th17 when present within a certain concentration range. Pyone 6 reduced the expression of IFN-γ and IL-13, while it enhanced the expression of IL-17 and IL-22. Pyridone6 also inhibited the development of Th1 and Th2, while it promoted the differentiation of Th17 from naïve T cells when present within a specific concentration range.

体内研究

Pyridone 6 (P6) can delay the onset and reduce the severity of AD-like skin disease models in NC/Nga mice.6-nano strongly ameliorates atopic dermatitis (AD) in NC/Nga mice, with its effects comparable to betamethasone valerate, commonly used drug also tested as a positive control. In contrast, PLGA nanoparticles (C-nano) containing gluconolactone did not seem to work.

激酶实验

细胞实验

动物实验

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

1.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.

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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