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Pyridone 6 Pan-JAK inhibitor

Catalog No.A3741
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10mM (in 1mL DMSO)
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Sample solution is provided at 25 µL, 10mM.

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Chemical structure

Pyridone 6

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Chemical Properties

Cas No. 457081-03-7 SDF Download SDF
Synonyms CMP 6; JAK Inhibitor
Chemical Name 2-(tert-butyl)-9-fluoro-1H-benzo[h]imidazo[4,5-f]isoquinolin-7(6H)-one
Canonical SMILES CC(C)(C)C(N1)=NC2=C1C3=C(C4=C2C=CNC4=O)C=C(F)C=C3
Formula C18H16FN3O M.Wt 309.34
Solubility >15.5mg/mL in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request


Pyridone 6 is a reversible and selective ATP-competitive inhibitor of Janus-activated kinases (JAK) with IC50 value of 1-15 nM [1].

JAK is a tyrosine kinase family that and a component of the JAK-STAT signaling pathway. The combination of cytokine (such as interleukin and interferon) or growth factor (such as GH and EGF) and the associated receptors leads to the dimerization of the receptors. The dimerization triggers the activation (autophosphorylation) of JAK which binds to the receptor. Subsequent phosphorylation of the receptor caused by the activated JAK attracts STAT to bind to the receptor and to be activated by JAK. At last, activated STAT enters the nucleus and regulates gene transcription. It is found that constitutive activation of JAK and STAT can promote abnormal cell proliferation. The inhibition of JAK is believed to be an effective therapy to treat for malignancies.

Pyridone 6 is a potent inhibitor of JAK. It inhibited the activities of JAK1, JAK2, JAK3 and TYK2 with IC50 values of 15 nM, 1 nM, 5 nM and 1 nM, respectively. Pyridone 6 is also a selective JAK inhibitor. It showed IC50 values of more than 130 nM when tested against other kinases [1, 2 and 3].

In B9 cells, treatment of pyridone 6 at concentration of 250 nM significantly decreased the phosphorylation of STAT3 induced by IL-6. Treatment of 1 μM almost completely inhibited the phosphorylation of STAT3. Besides that, Pyridone 6 suppressed cell proliferation with IC50 value of 250 nM. In U266 cells, pyridone 6 treatment caused a modest cell growth reduction and G1 arrest. It is consistent with that the growth of U266 is partially dependent on IL-6 signaling [1].

Pyridone 6 has low water solubility. Due to this, a polylactic acid formulation of pyridone 6 and glycolic acid has been applied in animal model. In mice model of atopic dermatitis, administration of pyridone 6 is found to have therapeutic activity through modifying Th cell differentiation and inhibiting mast cell function [2].

[1].  Pedranzini L, Dechow T, Berishaj M, et al. Pyridone 6, a pan-Janus–activated kinase inhibitor, induces growth inhibition of multiple myeloma cells. Cancer research, 2006, 66(19): 9714-9721.
[2].  Nakagawa R, Yoshida H, Asakawa M, et al. Pyridone 6, a pan-JAK inhibitor, ameliorates allergic skin inflammation of NC/Nga mice via suppression of Th2 and enhancement of Th17. The Journal of Immunology, 2011, 187(9): 4611-4620.
[3].  Kwak H B, Kim H S, Lee M S, et al. Pyridone 6, A Pan-Janus-Activated Kinase Inhibitor, Suppresses Osteoclast Formation and Bone Resorption through Down-Regulation of Receptor Activator of Nuclear Factor-. KAPPA. B (NF-. KAPPA. B) Ligand (RANKL)-Induced c-Fos and Nuclear Factor of Activated T Cells (NFAT) c1 Expression. Biological and Pharmaceutical Bulletin, 2009, 32(1): 45-50.