Pyridone 6 | CAS#457081-03-7 | JAK Inhibitor

MedKoo Cat#: 406781 | Name: Pyridone 6

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Pyridone 6

CAS#457081-03-7

Theoretical Analysis

MedKoo Cat#: 406781

Name: Pyridone 6

CAS#: 457081-03-7

Chemical Formula: C18H16FN3O

Exact Mass: 309.1277

Molecular Weight: 309.34

Elemental Analysis: C, 69.89; H, 5.21; F, 6.14; N, 13.58; O, 5.17

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,650.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,450.00	2 weeks
2g	USD 5,650.00	2 weeks

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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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# A21T09K29

QC Data

View QC data: current batch, Lot# A21T09K29

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	30.9	99.98
	Ethanol	15.5	50.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 309.34 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:

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.

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