SP-600125 (129-56-6) is a selective inhibitor of c-Jun N-terminal kinase (JNK). Reversibly inhibits JNK1,2 and 3 (IC50‘s range from 40-90 nM). >300-fold selectivity for JNK as compared to related MAP kinases. Anti-inflammatory activity. SP-600125 inhibits expression of presenilin-1 and Notch signaling in mouse brain. Cell permeable and active in vivo.
SP 600125 is a Jun N-terminal kinase (JNK) inhibitor.
A broad-spectrum serine/threonine kinase inhibitor of JNK with an IC50 range from 40 to 90 nM.
C2C12 myoblasts were treated with SP600125 to test the stimulation of myogenesis.11 It was used to treat HepG2 cells to test the effects on oxysterol-induced necrosis.12
ChEBI: A member of the class of anthrapyrazoles that is anthra[1,9-cd]pyrazole substituted at position 6 by an oxo group. An inhibitor of c-Jun N-terminal kinase.
A potent, cell-permeable, selective, and reversible inhibitor of c-Jun N-terminal kinase (JNK) (IC50 = 40 nM for JNK-1 and JNK-2 and 90 nM for JNK-3). The inhibition is competitive with respect to ATP. Exhibits over 300-fold greater selectivity for JNK as compared to ERK1 and p38-2 MAP kinases. Inhibits the phosphorylation of c-Jun and blocks the expression of IL-2, IFN-γ, TNF-α, and COX-2 in cells. Blocks IL-1-induced accumulation of phospho-Jun and induction of c-Jun transcription.
Selective inhibitor of c-Jun N-terminal kinase (JNK). Competitively and reversibly inhibits JNK1, 2 and 3 (IC 50 = 40-90 nM) with negligible activity at ERK2, p38 β and a range of enzymes (IC 50 > 10 μ M). Active in vivo . Shown to have reduced selectivity over other protein kinases under certain conditions. Protects renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis. Also available as part of the MAPK Inhibitor Tocriset™ .
SP600125 is an anthrapyrazolone inhibitor of JNK that competes with ATP to inhibit the phosphorylation of c-Jun. It prevents the activation of inflammatory genes such as COX-2, IL-2 IFN-γ and TNF-α.8,9 It prevents the activation of JNK after brain ischemia and may be effective in treatment of ischemic stroke.10
Poison by intravenous route.When heated to decomposition it emits toxic fumes ofNOx.
1,9-Pyrazolanthrone is prepared by diazotization
of 1-aminoanthraquinone, reaction of the
diazonium salt with sodium hydrogen sulfite,
and cyclization of the resulting hydrazinosulfonic
acid .
Novel, potent, and selective JNK-1,-2, and -3 inhibitor, SP600125 is an ATP-competetive inhibitor effective on a range of kinases and enzymes. 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. SP600125 has also 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.
[1] B L BENNETT. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase.[C]//19 1. 2001: 13681-13686. DOI:
10.1073/pnas.251194298[2] MOSHIUR RAHMAN . Intraperitoneal injection of JNK-specific inhibitor SP600125 inhibits the expression of presenilin-1 and Notch signaling in mouse brain without induction of apoptosis[J]. Brain Research, 2012, 1448: Pages 117-128. DOI:
10.1016/j.brainres.2012.01.066
