"目录号: HY-14435
EpigeneticsStem Cell/WntJAK/STAT Signaling-
Pyridone 6 是一种pan-JAK抑制剂，有效抑制 JAK 激酶家族，作用于JAK2，TYK2，JAK3和JAK1，IC50分别为 1 nM，1 nM，5 nM 和 15 nM。
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生物活性
Description
Pyridone 6 is apan-JAKinhibitor, which potently inhibits the JAK kinase family, withIC50s of 1 nM forJAK2andTYK2, 5 nM forJAK3, and 15 nM forJAK1, while displaying significantly weaker affinities (130 nM to >10 mM) for other protein tyrosine kinases.
IC50& Target
IC50: 1 nM (JAK2), 5 nM (JAK3), 15 nM (JAK1), 1 nM (TYK2)[1]
In Vitro
Pyridone 6 (P6) is shown to inhibit kinase by interacting within the ATP-binding cleft of each JAK. The IC50of 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[1]. Pyridone 6 inhibits osteoclast differentiation in mouse bone marrow macrophage (BMM) cultures stimulated by the receptor activator of nuclear factor-k B (NF-k B) ligand (RANKL) and co-cultures of bone marrow cells and osteoblasts. Pyridone 6 suppresses the expression of c-Fos and nuclear factor of activated T cells (NFAT) c1 in BMMs. Pyridone 6 also suppresses I-k B degradation and extracellular signal-regulated kinase (ERK) in mature osteoclasts, suggesting that these are the key molecules that pyridone 6 targets in the inhibition of osteoclast function[2]. Pyridone 6 (P6), is found to inhibit the JAKs in the low nanomolar range (IC50, 1-15 nM) and blocks IL-2-dependent proliferation of CTLL cells. Pyridone 6 is a reversible ATP inhibitor, and when tested against many other kinases, IC50s of >130 nM are required[3].
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 PLGA nanoparticles (C-nano) seemed to have no effect[1].
References
