JAK Inhibitor I

Janus-associated kinases (JAKs) are cytoplasmic tyrosine kinases that are required for activating the signaling of certain cytokines and growth factor receptors. JAK1 mostly activates IL-6, whereas JAK1 and JAK3 trigger IL-2 and IL-4 and JAK1 and JAK2 stimulates IFN-gamma. JAK Inhibitor I is a pyridine-containing tetracycle that interferes with JAK kinase activity by interacting within the ATP-binding cleft. It inhibits JAK1, 2, and 3 with IC50 values of 15, 1, and 5 nM, respectively, while displaying significantly weaker affinities (IC50s = 130 nM - > 10 µM) for other protein tyrosine kinases. It was shown to block IL-2 and IL-4-dependent proliferation of mouse T-cell lymphoma cells with IC50 values of 50-100 nM. In a mouse model of atopic dermatitis, JAK Inhibitor I, supplied at 2 mg encapsulated in a PLGA nanoparticle, was shown to suppress IFN-gamma/STAT1, IL-2/STAT5, and IL-4/STAT6 signaling pathways.Formal Name: 2-(1,1-dimethylethyl)-9-fluoro-1,6-dihydro-7H-benz[h]imidazo[4,5-f]isoquinolin-7-one. CAS Number: 457081-03-7. Synonyms: CMP 6, Janus-Associated Kinase Inhibitor I, Pyridone 6. Molecular Formula: C18H16FN3O. Formula Weight: 309.3. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 15 mg/ml, DMSO: 15 mg/ml, DMSO:PBS (pH 7.2) (1:2): 0.3 mg/ml, Ethanol: 1 mg/ml. lambdamax: 219, 260, 270, 328, 343, 359 nm. SMILES: O=C1NC=CC2=C1C(C=C(F)C=C3)=C3C4=C2NC(C(C)(C)C)=N4. InChi Code: InChI=1S/C18H16FN3O/c1-18(2,3)17-21-14-10-5-4-9(19)8-12(10)13-11(15(14)22-17)6-7-20-16(13)23/h4-8H,1-3H3,(H,20,23)(H,21,22). InChi Key: VNDWQCSOSCCWIP-UHFFFAOYSA-N.