| Identification | Back Directory | [Name]
AS-2444697 | [CAS]
1287665-60-4 | [Synonyms]
AS-244469
AS-2444697
AS-2444697 HC
AS-2444697 HCl
AS2444697 >=98% (HPLC)
AS-2444697 (hydrochloride)
FGNHLIIFEDYNFZ-UHFFFAOYSA-N
N-(3-CARBAMOYL-1-(TETRAHYDRO-2H-PYRAN-4-YL)-1H-PYRAZOL-4-YL)-2-(2-METHYLPYRIDIN-4-YL)OXAZOLE-4-CARBOXAMIDE HCL
N-(3-carbamoyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide hydrochloride
N-[3-Aminocarbonyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-2-(2-methyl-4-pyridinyl)-4-oxazolecarboxamide hydrochloride
4-Oxazolecarboxamide, N-[3-(aminocarbonyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-2-(2-methyl-4-pyridinyl)-, hydrochloride (1:1) | [Molecular Formula]
C19H21ClN6O4 | [MDL Number]
MFCD30182294 | [MOL File]
1287665-60-4.mol | [Molecular Weight]
432.861 |
| Chemical Properties | Back Directory | [storage temp. ]
2-8°C | [solubility ]
DMSO:16.83(Max Conc. mg/mL);38.88(Max Conc. mM) | [form ]
powder | [color ]
white to beige | [InChIKey]
FGNHLIIFEDYNFZ-UHFFFAOYSA-N | [SMILES]
O1C=C(C(NC2=CN(C3CCOCC3)N=C2C(=O)N)=O)N=C1C1C=CN=C(C)C=1.[H]Cl |
| Hazard Information | Back Directory | [Description]
AS-2444697 is an inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4; IC50 = 21 nM).1 It is greater than 30-fold selective for IRAK4 over a panel of 146 kinases, but is less than 10-fold selective over PDGFRα, PDGFRβ, TrkA, TrkC, CLK1, Itk, and FLT3. AS-2444697 inhibits IL-1β-induced IL-6 production and LPS-induced TNF-α production in cellular assays (IC50s = 250 and 47 nM, respectively). It is efficacious in rat models of adjuvant- and collagen-induced arthritis (ED50s = 2.7 and 1.6 mg/kg, respectively). AS-2444697 (0.3-3 mg/kg, twice daily) reduces urinary protein excretion, the development of interstitial fibrosis and glomerulosclerosis, and renal mRNA expression of genes encoding IL-1β, IL-6, TNF-α, and chemokine (C-C motif) ligand 2 (CCL2) without affecting blood pressure in the 5/6 nephrectomized rat model of chronic kidney disease.2 | [Uses]
AS2444697 has been used as an interleukin-1R-associated kinase 4 (IRAK4) inhibitor to study the role of interleukin (IL)-1/IL-33 signaling in the development of endometriosis using a mouse model of endometriosis. It has also been used to study its dose-dependent effect on the C-X-C motif chemokine ligand 8 (CXCL8) gene expression | [Biochem/physiol Actions]
AS2444697 is a potent and selective inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK-4) that suppresses the progression of chronic renal failure via anti-inflammatory action. | [in vivo]
AS2444697 is efficacious in the rat adjuvant-induced arthritis (ED50 2.7 mg/kg, BID, PO) and the rat collagen-induced arthritis (ED50 1.6 mg/kg, BID, PO) disease models. Good bioavailability was seen in rat (F% 50) and dog (F% 78) pharmacokinetic studies[1].
AS2444697 (0.3-3 mg/kg) significantly increases the plasma levels of IL-1β, IL-6, TNF-α, MCP-1, and aminotransferases (ALT and AST) in LPS/GalN-treated mice. Single administration of AS2444697 (0.3-3 mg/kg) dose-dependently decreases plasma levels of these all parameters, and these effects were significant at doses of 1 mg/kg or higher[2].
After oral administration of AS2444697 (3 mg/kg) to 5/6 Nx rats, plasma, and tissue (liver and kidney) concentrations of the unchanged drug peaked at 1 h and then gradually decreased, with a terminal half-life of 2.7-2.9 h[2].
| Animal Model: | Male 6-week-old Wistar rats and Balb/c mice[2] | | Dosage: | 0.3-3 mg/kg | | Administration: | Single administration; orally | | Result: | The plasma levels of IL-1β, IL-6, TNF-α, MCP-1, and aminotransferases (ALT and AST) were significantly increased. |
| [IC 50]
IRAK4: 21 nM (IC50) | [storage]
Desiccate at RT | [References]
[1] J. HYNES S N. Chapter Nine - Advances in the Discovery of Small-Molecule IRAK4 Inhibitors[J]. Annual Reports in Medicinal Chemistry, 2014, 49 1: 117-133. DOI: 10.1016/b978-0-12-800167-7.00009-2
[2] MITSUHIRO KONDO. Renoprotective effects of novel interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 through anti-inflammatory action in 5/6 nephrectomized rats.[J]. Naunyn-Schmiedeberg’s archives of pharmacology, 2014, 387 10: 909-919. DOI: 10.1007/s00210-014-1023-z |
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| Company Name: |
BOC Sciences
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| Tel: |
1-631-485-4226; 16314854226 |
| Website: |
https://www.bocsci.com |
| Company Name: |
Sigma-Aldrich
|
| Tel: |
021-61415566 800-8193336 |
| Website: |
https://www.sigmaaldrich.cn |
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