SP600125

SP600125 is an orally active, reversible and ATP-competitive broad-spectrum JNK inhibitor for JNK1, JNK2 and JNK3 (IC50 = 40nM, 40nM and 90nM, respectively). In Jurkat T cells, SP600125 suppressed the phosphorylation of c-Jun with IC50 of 5-10 µM. It has 10-fold greater selectivity against MKK4, 25-fold greater selectivity against MKK3, MKK6, PKB and PKCalpha, and 100-fold selectivity against ERK2, p38, Chk1, EGFR. SP600125 is also a broad-spectrum inhibitor of serine/threonine kinases including hydrocarbon receptor (AhR), Mps1, Aurora kinase A, FLT3 and TRKA. SP600125 inhibits cell cycle, autophagy and ferroptosis and activates apoptosis. It shows anti-inflammatory activity by inhibiting the expression of inflammatory genes such as COX-2, IL-2 IFN-gamma and TNF-alpha and has antiviral and neuroprotective properties. SP600125 demonstrated inhibitory effects on tumor cell proliferation, endothelial cell migration and tumor growth as well as blocking tumor and endothelial cells in the G2 phase of the cell cycle. SP600125 also promotes adipogenesis from MSCs and is an essential component of media for maintaining stem cells in naive pluripotent state. JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation. The JNK1 inhibitor SP600125 exhibits a robust inhibition of inflammasome activation.