WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406781
CAS#: 457081-03-7
Description: 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.
MedKoo Cat#: 406781
Name: Pyridone 6
CAS#: 457081-03-7
Chemical Formula: C18H16FN3O
Exact Mass: 309.1277
Molecular Weight: 309.3444
Elemental Analysis: C, 69.89; H, 5.21; F, 6.14; N, 13.58; O, 5.17
Synonym: Pyridone 6; Pyridone-6; Pyridone6; CMP 6; JAK Inhibitor I; Janus-Associated Kinase Inhibitor I.
IUPAC/Chemical Name: 2-(1,1-dimethylethyl)-9-fluoro-1,6-dihydro-7H-benz[h]imidazo[4,5-f]isoquinolin-7-one
InChi Key: VNDWQCSOSCCWIP-UHFFFAOYSA-N
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)
SMILES Code: O=C1NC=CC2=C1C3=CC(F)=CC=C3C4=C2N=C(C(C)(C)C)N4
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Pyridone 6 is a potent pan-JAK inhibitor; ATP-competitive inhibitor of JAK 1/2/3 and Tyk2 |
| In vitro activity: | In this study, the effects of a pan-JAK inhibitor, pyridone 6, on osteoclast differentiation and bone-resorption in vitro and ex vivo were investigated. Pyridone 6 inhibited osteoclast differentiation in mouse bone marrow macrophage (BMM) cultures stimulated by the receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL) and co-cultures of bone marrow cells and osteoblasts. Pyridone 6 suppressed the expression of c-Fos and nuclear factor of activated T cells (NFAT) c1 in BMMs. It also inhibited the bone resorptive activity of mature osteoclasts that was accompanied by disruption of actin rings. Pyridone 6 also suppressed I-kappaB 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. These results demonstrate inhibition of JAK may be useful for the treatment of bone-resorptive diseases, such as osteoporosis. Reference: 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. doi: 10.1248/bpb.32.45. PMID: 19122279. |
| In vivo activity: | In the current study, pyridone 6 (P6), a pan-JAK inhibitor, delayed the onset and reduced the magnitude of skin disease in an AD-like skin-disease model of NC/Nga mice. P6 reduced IFN-γ and IL-13, whereas it enhanced IL-17 and IL-22 expression. In vitro, P6 also inhibited both Th1 and Th2 development, whereas it promoted Th17 differentiation from naive T cells when present within a certain range of concentrations. This was probably because P6 strongly inhibited STAT1, STAT5, and STAT6 phosphorylation, whereas STAT3 phosphorylation was less efficiently suppressed by P6 at the same concentration. Furthermore, IL-22 protects keratinocytes from apoptosis induced by IFN-γ, and administration of IL-17 and IL-22 partially ameliorated skin diseases in NC/Nga mice. These results suggested that the JAK inhibitor P6 is therapeutic for AD by modulating the balance of Th2 and Th17. Reference: 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. PMID: 21957150. |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 30.93 | 99.98 | |
| Ethanol | 15.47 | 50.0 |
The following data is based on the product molecular weight 309.3444 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 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. doi: 10.1248/bpb.32.45. PMID: 19122279. |
| In vitro protocol: | 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. doi: 10.1248/bpb.32.45. PMID: 19122279. |
| In vivo protocol: | 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. PMID: 21957150. |
1: 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.
2: Matsunaga Y, Inoue H, Fukuyama S, Yoshida H, Moriwaki A, Matsumoto T,
Matsumoto K, Asai Y, Kubo M, Yoshimura A, Nakanishi Y. Effects of a Janus kinase
inhibitor, pyridone 6, on airway responses in a murine model of asthma. Biochem
Biophys Res Commun. 2011 Jan 7;404(1):261-7. doi: 10.1016/j.bbrc.2010.11.104.
Epub 2010 Nov 25. PubMed PMID: 21111712.
3: 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.
4: 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.
