SP600125 is a reversible, ATP-competitive inhibitor of Jun N-terminal kinase (JNK), with a Ki of 0.19 µM. It selectively inhibits JNK1, -2, and -3, showing greater than 300-fold selectivity over related kinases such as ERK1 and p38-2. In cell-based assays, SP600125 inhibits the phosphorylation of c-Jun, reduces the expression of inflammatory genes like COX-2, IL-2, IFN-γ, and TNF-α, and prevents the activation and differentiation of primary human CD4+ cells. In animal studies, SP600125 blocks LPS-induced TNF-α expression and inhibits CD3-induced apoptosis of CD4+ CD8+ thymocytes. These findings support the therapeutic potential of JNK inhibition in inflammatory diseases, apoptosis, and cancer. SP600125 selectively inhibits inflammatory gene expression, including TNF-α, and reduces mRNA half-life, suggesting a role in mRNA stabilization. It also exhibits anti-apoptotic effects in thymocytes, consistent with JNK's role in cell death. SP600125 shows efficacy in models of arthritis and lung inflammation. It is not a strong DNA chelator and does not induce apoptosis. JNK inhibition may have clinical benefits in diseases involving cell death, including stroke and Parkinson's disease. Overall, SP600125 is a selective JNK inhibitor with potential therapeutic applications in inflammatory and neurodegenerative diseases.SP600125 is a reversible, ATP-competitive inhibitor of Jun N-terminal kinase (JNK), with a Ki of 0.19 µM. It selectively inhibits JNK1, -2, and -3, showing greater than 300-fold selectivity over related kinases such as ERK1 and p38-2. In cell-based assays, SP600125 inhibits the phosphorylation of c-Jun, reduces the expression of inflammatory genes like COX-2, IL-2, IFN-γ, and TNF-α, and prevents the activation and differentiation of primary human CD4+ cells. In animal studies, SP600125 blocks LPS-induced TNF-α expression and inhibits CD3-induced apoptosis of CD4+ CD8+ thymocytes. These findings support the therapeutic potential of JNK inhibition in inflammatory diseases, apoptosis, and cancer. SP600125 selectively inhibits inflammatory gene expression, including TNF-α, and reduces mRNA half-life, suggesting a role in mRNA stabilization. It also exhibits anti-apoptotic effects in thymocytes, consistent with JNK's role in cell death. SP600125 shows efficacy in models of arthritis and lung inflammation. It is not a strong DNA chelator and does not induce apoptosis. JNK inhibition may have clinical benefits in diseases involving cell death, including stroke and Parkinson's disease. Overall, SP600125 is a selective JNK inhibitor with potential therapeutic applications in inflammatory and neurodegenerative diseases.