SP600125

• CAT Number: I001134
• CAS Number: 129-56-6
• Molecular Formula: C₁₄H₈N₂O
• Molecular Weight: 220.23
• Purity: ≥95%
• Target: JNK
• Solubility: DMSO: ≥ 45 mg/mL
• Storage: 3 years -20C powder
• IC50: 40/40/90 nM(JNK1/2/3) [1]
• InChI: InChI=1S/C14H8N2O/c17-14-9-5-2-1-4-8(9)13-12-10(14)6-3-7-11(12)15-16-13/h1-7H,(H,15,16)
• InChIKey: ACPOUJIDANTYHO-UHFFFAOYSA-N
• SMILES: C1=CC=C2C(=C1)C3=NNC4=CC=CC(=C43)C2=O

SP600125 is a broad-spectrum JNK inhibitor for JNK1, JNK2 and JNK3 with IC50 of 40 nM, 40 nM and 90 nM, respectively; 10-fold greater selectivity against MKK4, 25-fold greater selectivity against MKK3, MKK6, PKB, and PKCα, and 100-fold selectivity against ERK2, p38, Chk1, EGFR etc.IC50 value: 40/40/90 nM(JNK1/2/3) [1]Target: JNKin vitro: SP600125 is originally characterized as a selective ATP-competitive inhibitor of c-Jun N-terminal kinase JNK. In Jurkat T cells, SP600125 inhibits the phosphorylation of c-Jun with IC50 of 5 μM to 10 μM. In CD4+ cells, such as Th0 cells isolated from either human cord or peripheral blood, SP600125 blocks cell activation and differentiation and inhibits the expression of inflammatory genes COX-2, IL-2, IL-10, IFN-γ, and TNF-α, with IC50 of 5 μM to 12 μM [1]. In a mouse beta cells MIN6, SP600125 (20 μM) induces the phosphorylation of p38 MAPK and its downstream CREB-dependent promoter activation [2]. n HCT116 cells, SP600125 (20 μM) blocks the G2 phase to mitosis transition and induces endoreplication. This ability of SP600125 is independent of JNK inhibition, but due to its inhibition of CDK1-cyclin B activation upstream of Aurora A and Polo-like kinase 1 [3].in vivo: In mice, SP600125 (15 mg/kg or 30 mg/kg) significantly inhibits lipopolysaccharide (LPS)-induced TNF-α expression and anti-CD3-induced apoptosis of CD4+ CD8+ thymocytes [1].

Reference

1:JNK Inhibitor SP600125 Attenuates Paraquat-Induced Acute Lung Injury: an In Vivo and In Vitro Study. Shen H, Wu N, Wang Y, Han X, Zheng Q, Cai X, Zhang H, Zhao M.Inflammation. 2017 May 4. doi: 10.1007/s10753-017-0575-8. [Epub ahead of print] PMID: 28474156 2:Effect of SP600125 on the mitotic spindle in HeLa Cells, leading to mitotic arrest, endoreduplication and apoptosis. Mili D, Abid K, Rjiba I, Kenani A.Mol Cytogenet. 2016 Nov 25;9:86. eCollection 2016. PMID: 27924151 Free PMC Article3:SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration. Guo ZZ, Cao QA, Li ZZ, Liu LP, Zhang Z, Zhu YJ, Chu G, Dai QY.Mediators Inflamm. 2016;2016:9142425. Epub 2016 Sep 1. PMID: 27688602 Free PMC Article4:[SP600125-induced polyploidization of megakaryocytic leukemia cell lines by ribosomal protein S6 kinase 1 depends on the degree of cell differentiation]. Wang L, Yang J, Li C, Xing S, Yu Y, Liu S, Zhao S, Ma D.Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016 Oct;32(10):1336-1341. Chinese. PMID: 27667458 5:[Protein kinase A inhibitor H-89 blocks polyploidization of SP600125-induced CMK cells by regulating phosphorylation of ribosomal protein S6 kinase 1]. Zhao S, Yang J, Li C, Xing S, Yu Y, Liu S, Pu F, Ma D.Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016 Oct;32(10):1321-1326. Chinese. PMID: 27667455 6:Effect of JNK inhibitor SP600125 on hair cell regeneration in zebrafish (Danio rerio) larvae. He Y, Cai C, Sun S, Wang X, Li W, Li H.Oncotarget. 2016 Aug 9;7(32):51640-51650. doi: 10.18632/oncotarget.10540. PMID: 27438150 Free PMC Article7:SP600125 enhances the anti-apoptotic capacity and migration of bone marrow mesenchymal stem cells treated with tumor necrosis factor-α. Wei B, Bai X, Chen K, Zhang X.Biochem Biophys Res Commun. 2016 Jul 8;475(4):301-7. doi: 10.1016/j.bbrc.2016.05.107. Epub 2016 May 24. PMID: 27233606 8:Autotetraploid cell line induced by SP600125 from crucian carp and its developmental potentiality. Zhou Y, Wang M, Jiang M, Peng L, Wan C, Liu J, Liu W, Zhao R, Zhao X, Hu W, Liu S, Xiao Y.Sci Rep. 2016 Feb 22;6:21814. doi: 10.1038/srep21814. PMID: 26898354 Free PMC Article9:SP600125 has a remarkable anticancer potential against undifferentiated thyroid cancer through selective action on ROCK and p53 pathways. Grassi ES, Vezzoli V, Negri I, Lábadi Á, Fugazzola L, Vitale G, Persani L.Oncotarget. 2015 Nov 3;6(34):36383-99. doi: 10.18632/oncotarget.5799. PMID: 26415230 Free PMC Article10:SP600125 promotes resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model. Wu HM, Fang L, Shen QY, Liu RY.Mol Immunol. 2015 Oct;67(2 Pt B):311-6. doi: 10.1016/j.molimm.2015.06.016. Epub 2015 Jun 29. PMID: 26139014