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DBM1285 Suppresses TNF-a Production via p38 MAPK Signaling Pathway

DBM1285, a novel compound, inhibits tumor necrosis factor-a by targeting p38 MAPK/ MAPK-activated protein kinase 2 pathway. In this study, the effect of DBM1285 on LPS-induced TNF-a mRNA expression and p38 MAPK phosphorylation in RAW 264.7 cells was investigated. Results show a dose-dependent reduction in TNF-a mRNA expression and p38 MAPK phosphorylation upon treatment with DBM1285.

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DBM1285 Suppresses TNF-a Production via p38 MAPK Signaling Pathway

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  1. DBM1285 [cyclopropyl-{4-[4-(4-fluorophenyl)-2-piperidin-4-yl-thiazol-5-yl]pyrimidin-2-yl}amine] suppresses tumor necrosis factor-a production by blocking p38 mitogen-activated protein kinase/mitogen-activated protein kinase-activated protein kinase 2 signaling pathway, Kang JS, Kim HM, Choi IY, Han SB, Yoon YD, Lee H, Park KH, Cho IG, Lee CW, Lee K, Lee KH and Park SK, Journal of Pharmacology and Experimental Therapeutics Supplementary Fig. 2 A B LPS (1 mg/ml) + DBM1285 (mM) LPS (1 mg/ml) + DBM1285 (mM) UN VH 0.01 0.1 1 UN VH 0.001 0.01 0.1 1 TNF-a p-p38 MAPK b-actin Effect of DBM1285 on LPS-induced TNF-a mRNA expression and p38 MAPK phosphorylation in RAW 264.7 cells. RAW 264.7 cells were plated at 5 X 105 cells/ml. Vehicle (VH, DMSO) or indicated concentrations of DBM1285 (0.001, 0.01, 0.1 or 1 mM) was pretreated for 1 h before being incubated with LPS (1 mg/ml) for 6 h or 30 min. (A) Total RNAs were isolated and the mRNA expression of TNF-a and b-actin was determined by RT-PCR. (B) Total cell lysates were prepared and phosphorylated forms of p38 MAPK was detected by Western immunoblot analysis.

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