SP 600125
SP600125 is a selective, reversible and ATP-competitive inhibitor of Jun N-terminal kinase (JNK) with IC50 values of 40, 40 and 90 nM for JNK1, 2 and 3, respectively [1].
SP600125 was screened out from a time-resolved f luorescence assay using the GST-c-Jun and recombinant human JNK2. In this assay, SP600125 showed a Ki value of 190 nM. SP600125 was also found to inhibit JNK1, 2 and 3 isoforms in the selectivity tests. The selectivity of SP600125 for JNK is 300-fold greater than that for ERK1 and p38-2. In Jurkat T cells, SP600125 suppressed the phosphorylation of c-Jun with IC50 of 5-10 μM. SP600125 also inhibited the expression of IL-2 and IFN-γ in cells stimulated with PMA and phytohemagglutinin, since JNK had been reported to regulate the transcription of IL-2. Besides that, SP600125 exerted differential inhibition of cytokines in CD4+ cells as well as inflammatory genes in monocytes. Moreover, SP600125 administration significantly inhibited TNF-α expression induced by LPS in a mouse model, suggesting that it had efficacy in endotoxin-induced inf lammation in vivo [1].
References:
[1] Bennett B L, Sasaki D T, Murray B W, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proceedings of the National Academy of Sciences, 2001, 98(24): 13681-13686.
- 1. Zhao Wang, Kristin Franke, et al. "MRGPRX2-Mediated Degranulation of Human Skin Mast Cells Requires the Operation of Gαi, Gαq, Ca++ Channels, ERK1/2 and PI3K—Interconnection between Early and Late Signaling." Cells. 2022 Mar 10;11(6):953. PMID: 35326404
- 2. Li Zhang, Lei Cheng, et al. "The virulence factor GroEL directs the osteogenic and adipogenic differentiation of human periodontal ligament stem cells through the involvement of JNK/MAPK and NF-κB signaling." J Periodontol. 2021 Nov;92(11):103-115. PMID: 33913537
- 3. Yuliu Zhang, Jianping Du, et al. "RIPK1 contributes to cisplatin-induced apoptosis of esophageal squamous cell carcinoma cells via activation of JNK pathway." Life Sci. 2021 Mar 15;269:119064. PMID: 33460665
- 4. Jian-Wei Hao, Juan Wang, et al. "CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis." Nat Commun. 2020 Sep 21;11(1):4765. PMID: 32958780
- 5. Jingman Li, Yuchen Pan, et al. "Urokinase-type plasminogen activator receptor is required for impairing toll-like receptor 7 signaling on macrophage efferocytosis in lupus." Mol Immunol. 2020 Nov;127:38-45. PMID: 32911323
- 6. Yang PM, Hong YH, et al. "Progressive Rotavirus Infection Downregulates Redox-Sensitive Transcription Factor Nrf2 and Nrf2-Driven Transcription Units." Oxid Med Cell Longev. 2020 Apr 4;2020:7289120. PMID: 32322337
- 7. Chen X, Lao Y, et al. "SENP3 in monocytes/macrophages up-regulates tissue factor and mediates lipopolysaccharide-induced acute lung injury by enhancing JNK phosphorylation." J Cell Mol Med. 2020;24(10):5454-5462. PMID: 32237051
- 8. Ruibin Bai, Yajie Zhang, et al. "Isolation, characterization and immunomodulatory activity of oligosaccharides from Codonopsis pilosula." Journal of Functional Foods. Volume 72, September 2020, 104070
- 9. Liu B, Shen LJ, et al. "Automobile exhaust-derived PM(2.5) induces blood-testis barrier damage through ROS-MAPK-Nrf2 pathway in sertoli cells of rats." Ecotoxicol Environ Saf. 2020 Feb;189:110053. PMID: 31862514
- 10. Mitchell DC, Menon A, et al. "Cyclin-dependent kinase 4 inhibits the translational repressor 4E-BP1 to promote cap-dependent translation during mitosis-G1 transition." FEBS Lett. 2020 Apr;594(8):1307-1318. PMID: 31853978
- 11. Bhattacharya U, Gutter-Kapon L, et al. "Heparanase and Chemotherapy Synergize to Drive Macrophage Activation and Enhance Tumor Growth." Cancer Res. 2020 Jan 1;80(1):57-68. PMID: 31690669
- 12. Hazzan T, Eberle J, et al. "Thymic Stromal Lymphopoietin Interferes with the Apoptosis of Human Skin Mast Cells by a Dual Strategy Involving STAT5/Mcl-1 and JNK/Bcl-x(L)." Cells. 2019 Aug 5;8(8). pii: E829. PMID: 31387206
- 13. Wang Z, Chen J, et al. "cGAS/STING axis mediates a topoisomerase II inhibitor-induced tumor immunogenicity." J Clin Invest. 2019 Aug 13;130:4850-4862. PMID: 31408442
- 14. Dylan Charles Mitchell. "Development of a Chemoproteomic Approach to Study Kinase-Substrate Interactions and the Discovery of CDK4 as a 4E-BP1 Kinase." University of Michigan. 2019.
- 15. Liu W, Zhan C, et al. "Microcystin-LR influences the in vitro oocyte maturation of zebrafish by activating the MAPK pathway." Aquat Toxicol. 2019 Oct;215:105261. PMID: 31419757
- 16. Wang Z, Guhl S, et al. "IL-33 and MRGPRX2-Triggered Activation of Human Skin Mast Cells-Elimination of Receptor Expression on Chronic Exposure, but Reinforced Degranulation on Acute Priming." Cells. 2019 Apr 11;8(4). pii: E341. PMID: 30979016
- 17. Wang Q, Zhou C, et al. "The involvement of the ERK-MAPK pathway in TGF-β1-mediated connexin43-gap junction formation in chondrocytes. Connect Tissue Res." 2019 Mar 22:1-10. PMID: 30897973
- 18. Vincent Picher-Martel. "L’implication de l’ubiquiline-2 dans l’agrégation de TDP-43 et la pathogénèse de la sclérose latérale amyotrophique." University Laval. 2019.
- 19. Wang Y, Li Y, et al. "The cerebral cavernous malformation disease causing gene KRIT1 participates in intestinal epithelial barrier maintenance and regulation." FASEB J. 2018 Sep 25:fj201800343R. PMID: 30252535
- 20. MXinwei Feng1, Junfeng Lu2, et al. "Mycobacterium smegmatis Induces Neurite Outgrowth and Differentiation in an Autophagy-Independent Manner in PC12 and C17.2 Cells." Front. Cell. Infect. Microbiol., 19 June 2018.
- 21. Sharma K, Vu TT, et al. "p53-independent Noxa induction by cisplatin is regulated by ATF3/ATF4 in head and neck squamous cell carcinoma cells." Mol Oncol. 2018 Jan 19. PMID: 29352505
- 22. He GR, Lin XK, et al. "Dexmedetomidine impairs Pglycoprotein mediated efflux function in L02 cells via the denosine5'monophosphate activated protein kinase/nuclear factor κB pathway." Mol Med Rep.2018 Apr;17(4):5049-5056. PMID: 29393492
| Physical Appearance | A solid |
| Storage | Desiccate at -20°C |
| M.Wt | 220.23 |
| Cas No. | 129-56-6 |
| Formula | C14H8N2O |
| Solubility | insoluble in H2O; ≥11 mg/mL in DMSO; ≥2.56 mg/mL in EtOH with gentle warming |
| Chemical Name | dibenzo[cd,g]indazol-6(2H)-one |
| SDF | Download SDF |
| Canonical SMILES | O=C1C2=CC=CC3=C2C(C4=CC=CC=C41)=NN3 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
MIN6 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
40 μM, 36 hours |
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Applications |
When the MIN6 cells were transfected with the Gal4 plasmid and CREB plasmid, SP600125 significantly stimulated CREB-mediated promoter activity in a dose-dependent manner. There was a 2.8-fold increase in this reporter activity after exposure of the transfected MIN6 cells to 20 μM of the inhibitor. |
| Animal experiment: [2] | |
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Animal models |
Female C57BL/6 mice |
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Dosage form |
Subcutaneous injection; 15 mg/kg; administered at 0, 12, 24, and 36 h |
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Applications |
Anti-CD3 (50 μg) i.p. was administered as a single dose immediately after SP600125 at time 0. After 48 h, mice were killed, and the thymus was dissected for thymocyte isolation. Mice receiving SP600125 showed almost complete resistance to CD3 Ab-mediated apoptosis with CD4+CD8+ numbers the same as control animals. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Vaishnav D, Jambal P, Reusch J E B, et al. SP600125, an inhibitor of c-jun N-terminal kinase, activates CREB by a p38 MAPK-mediated pathway. Biochemical and biophysical research communications, 2003, 307(4): 855-860. [2] Bennett B L, Sasaki D T, Murray B W, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proceedings of the National Academy of Sciences, 2001, 98(24): 13681-13686. |
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| Description | SP600125 is a broad-spectrum inhibitor of JNK for JNK1, JNK2 and JNK3 with IC50 of 40 nM, 40 nM and 90 nM, respectively. | |||||
| Targets | JNK1 | JNK2 | JNK3 | Aurora A | Flt3 | TRKA |
| IC50 | 40 nM | 40 nM | 90 nM | 60 nM | 90 nM | 70 nM |
Quality Control & MSDS
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