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Novel, potent and selective JNK-1,-2, and -3 inhibitor (Ki = 0.19 µM). SP600125 is an ATP-competitive reversible inhibitor with >20-fold selectivity vs. a range of kinases and enzymes tested. In cells, SP600125 caused a dose-dependent inhibition of the phosphorylation of c-Jun, the expression of inflammatory genes IL-2, COX-2, TNF-α, IFN-γ, and blocked the activation and differentiation of primary human CD4 cell cultures.