SP600125

SP600125 is a selective, ATP-competitive JNK inhibitor. SP600125 reversibly inhibits JNK1, 2 and 3 (IC50 = 40 - 90 nM) with negligible activity at ERK2, p38beta and a range of enzymes (IC50 > 10 uM). SP600125 potently decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion via suppression of the extrinsic pathway. In cells, SP600125 dose dependently inhibited the phosphorylation of c-Jun, the expression of inflammatory genes COX-2, IL-2, IFN-gamma, TNF-alpha, and prevented the activation and differentiation of primary human CD4 cell cultures. In mice, SP600125 (15 mg/kg or 30 mg/kg) blocked lipopolysaccharide (LPS)-induced TNF-alpha expression and anti-CD3-induced apoptosis of CD4(+) CD8(+) thymocytes.