MERcK-5

Pyridone 6, also known CMP 6 or JAK Inhibitor I, is a pan-Janus-activated kinase inhibitor, Pyridone 6 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. Pyridone 6 suppresses osteoclast formation and bone resorption through down-regulation of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced c-Fos and nuclear factor of activated T cells (NFAT) c1 expression. Pyridone 6 induces growth inhibition of multiple myeloma cells.

Product information

CAS Number: 457081-03-7

Molecular Weight: 309.34

Formula: C18H16FN3O

Synonym:

Pyridone-6

JAK Inhibitor I

Janus-Associated Kinase Inhibitor I

CMP 6

Pyridone 6

Pyridone6

Chemical Name: 2-(1,1-dimethylethyl)-9-fluoro-1,6-dihydro-7H-benz[h]imidazo[4,5-f]isoquinolin-7-one

Smiles: CC(C)(C)C1NC2=C(N=1)C1C=CNC(=O)C=1C1=CC(F)=CC=C12

InChiKey: VNDWQCSOSCCWIP-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

MERcK-5 is tested as an inhibitor of 21 other protein kinases; MERcK-5 inhibits these kinases with IC50s ranging from 130 nM to >10 μM. MERcK-5 inhibits IL2 driven proliferation of CTLL cells with IC50=0.1 μM and IL4 driven proliferation with IC50=0.052 μM. MERcK-5 (P6) is shown to inhibit kinase by interacting within the ATP-binding cleft of each JAK. The IC50 of MERcK-5 is 3 nM for all of these cytokines; this is comparable to the reported IC50s of MERcK-5 for JAK2, Tyk2, and JAK3. MERcK-5 strongly inhibits Th2 and modestly inhibits Th1, whereas it enhances Th17 development when present within a certain range of concentrations. MERcK-5 reduces IFN-γ and IL-13, whereas it enhances IL-17 and IL-22 expression. MERcK-5 also inhibits both Th1 and Th2 development, whereas it promotes Th17 differentiation from naive T cells when present within a certain range of concentrations.

In Vivo:

MERcK-5 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.

References:

1. Pedranzini L, Dechow T, Berishaj M, Comenzo R, Zhou P, Azare J, Bornmann W, Bromberg J. Pyridone 6, a pan-Janus-activated kinase inhibitor, induces growth inhibition of multiple myeloma cells. Cancer Res. 2006 Oct 1;66(19):9714-21. PubMed PMID: 17018630.
2. Kwak HB, Kim HS, Lee MS, Kim KJ, Choi EY, Choi MK, Kim JJ, Cho HJ, Kim JW, Bae JM, Kim YK, Park BH, Ha H, Chun CH, Oh J. Pyridone 6, a pan-Janus-activated kinase inhibitor, suppresses osteoclast formation and bone resorption through down-regulation of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced c-Fos and nuclear factor of activated T cells (NFAT) c1 expression. Biol Pharm Bull. 2009 Jan;32(1):45-50. PubMed PMID: 19122279.
3. Nakagawa R, Yoshida H, Asakawa M, Tamiya T, Inoue N, Morita R, Inoue H, Nakao A, Yoshimura A. 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. doi: 10.4049/jimmunol.1100649. Epub 2011 Sep 28. PubMed PMID: 21957150.

Products are for research use only. Not for human use.