Selective inhibitors of tumor progression loci-2 (Tpl2) kinase with potent inhibition of TNF-α production in human whole blood

Tpl2 (cot/MAP3K8) is an upstream kinase of MEK in the ERK pathway. It plays an important role in Tumor Necrosis Factor-α (TNF-α) production and signaling. We have discovered that 8-halo-4-(3-chloro-4-fluoro-phenylamino)-6-[(1 H-[1,2,3]triazol-4-ylmethyl)-amino]-quinoline-3-carbonitriles ( 4) are pot...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009-07, Vol.19 (13), p.3485-3488
Hauptverfasser:	Wu, Junjun, Green, Neal, Hotchandani, Rajeev, Hu, Yonghan, Condon, Jeffrey, Huang, Adrian, Kaila, Neelu, Li, Huan-Qiu, Guler, Satenig, Li, Wei, Tam, Steve Y., Wang, Qin, Pelker, Jeffrey, Marusic, Suzana, Hsu, Sang, Perry Hall, J., Telliez, Jean-Baptiste, Cui, Junqing, Lin, Lih-Ling
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Anti-Inflammatory Agents - chemical synthesis Anti-Inflammatory Agents - chemistry Anti-Inflammatory Agents - pharmacokinetics Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Female Humans Lipopolysaccharides - pharmacology MAP Kinase Kinase Kinases - antagonists & inhibitors MAP Kinase Kinase Kinases - metabolism Medical sciences Monocytes - drug effects Monocytes - immunology Nitriles - chemical synthesis Nitriles - chemistry Nitriles - pharmacokinetics Pharmacology. Drug treatments Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacokinetics Proto-Oncogene Proteins - antagonists & inhibitors Proto-Oncogene Proteins - metabolism Quinoline-3-carbonitrile Quinolines - chemical synthesis Quinolines - chemistry Quinolines - pharmacokinetics Rats Rats, Sprague-Dawley TNF-α Tpl2 kinase Triazole Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - blood
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