WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 510239
Description: AS1940477 is p38 MAPK inhibitor. AS1940477 inhibited the enzymatic activity of recombinant p38α and β isoforms but showed no effect against other 100 protein kinases including p38γ and δ isoforms. In human peripheral blood mononuclear cells, AS1940477 inhibited lipopolysaccharide (LPS)- or phytohemagglutinin A (PHA)-induced production of proinflammatory cytokines, including TNFα, IL-1β, and IL-6 at low concentrations (LPS/TNFα, IC(50)=0.45n M; PHA/TNFα, IC(50)=0.40 nM). In addition, equivalent concentrations of AS1940477 that inhibited cytokine production also inhibited TNFα- and IL-1 β-induced production of IL-6, PGE(2), and MMP-3 in human synovial stromal cells. AS1940477 was also found to potently inhibit TNF production in whole blood (IC(50)=12 nM) and effectively inhibited TNFα production induced by systemically administered LPS in rats at less than 0.1mg/kg (ED(50)=0.053 mg/kg) with an anti-inflammatory effect lasting for 20h after oral administration. Overall, this study demonstrated that AS1940477 is a novel and potent p38 MAPK inhibitor and may be useful as a promising anti-inflammatory agent for treating inflammatory disorders.
MedKoo Cat#: 510239
Chemical Formula: C24H22FN5O2
Exact Mass: 431.17575
Molecular Weight: 431.46218
Elemental Analysis: C, 66.81; H, 5.14; F, 4.40; N, 16.23; O, 7.42
Synonym: AS1940477; AS-1940477; AS 1940477
IUPAC/Chemical Name: (R)-6-(2-(4-fluorophenyl)-6-(hydroxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)-2-(o-tolyl)pyridazin-3(2H)-one
InChi Key: LYHNSWOZRDSWLX-MRXNPFEDSA-N
InChi Code: InChI=1S/C24H22FN5O2/c1-15-4-2-3-5-20(15)30-21(32)11-10-19(27-30)22-23(17-6-8-18(25)9-7-17)28-29-13-16(14-31)12-26-24(22)29/h2-11,16,26,31H,12-14H2,1H3/t16-/m1/s1
SMILES Code: O=C1C=CC(C2=C3NC[C@@H](CO)CN3N=C2C4=CC=C(F)C=C4)=NN1C5=CC=CC=C5C
1: Terajima M, Inoue T, Magari K, Yamazaki H, Higashi Y, Mizuhara H. Anti-inflammatory effect and selectivity profile of AS1940477, a novel and potent p38 mitogen-activated protein kinase inhibitor. Eur J Pharmacol. 2013 Jan 5;698(1-3):455-62. doi: 10.1016/j.ejphar.2012.11.021. Epub 2012 Nov 23. PubMed PMID: 23183108.
2: Asano T, Yamazaki H, Kasahara C, Kubota H, Kontani T, Harayama Y, Ohno K, Mizuhara H, Yokomoto M, Misumi K, Kinoshita T, Ohta M, Takeuchi M. Identification, synthesis, and biological evaluation of 6-[(6R)-2-(4-fluorophenyl)-6-(hydroxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyr imidin-3-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one (AS1940477), a potent p38 MAP kinase inhibitor. J Med Chem. 2012 Sep 13;55(17):7772-85. doi: 10.1021/jm3008008. Epub 2012 Aug 31. PubMed PMID: 22905713.