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    SP600125 (SP600125; NSC75890)
    SP600125 (SP600125; NSC75890)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0471
    CAS #: 129-56-6Purity ≥98%

    Description: SP600125 (SP6-00125; NSC-75890) is a cell-permeable, broad-spectrum, reversible and ATP-competitive JNK (c-Jun N-terminal Kinase) inhibitor with potential anticancer and anti-inflammatory activity. It inhibits JNK1/2/3 with IC50s of 40 nM, 40 nM and 90 nM in cell-free assays, respectively. It shows potent anti-proliferative activity in vitro and high in vivo antitumor efficacy. SP600125 administration significantly inhibited TNF-α expression induced by LPS in a mouse model, suggesting that it had efficacy in endotoxin-induced inflammation in vivo.

    References: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13681-6; Cancer Res. 2010 Dec 15;70(24):10255-64.

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    Molecular Weight (MW)220.23
    CAS No.129-56-6
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 44 mg/mL (199.8 mM)
    Water: <1 mg/mL
    Ethanol:<1 mg/mL
    Solubility (In vivo)5% DMSO+corn oil: 5 mg/mL

    SP 600125; SP-600125; SP600125

    Chemical Name: dibenzo[cd,g]indazol-6(2H)-one


    InChi Code: 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)

    SMILES Code: O=C1C2=C3C(NN=C3C4=CC=CC=C14)=CC=C2 

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    In Vitro

    In vitro activity: 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. However, later studies reveal that SP600125 also suppresses aryl hydrocarbon receptor (AhR), Mps1, and a panel of other serine/threonine kinases, including Aurora kinase A, FLT3, MELK, and TRKA. In a mouse beta cells MIN6, SP600125 (20 μM) induces the phosphorylation of p38 MAPK and its downstream CREB-dependent promoter activation. In 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.

    Kinase Assay: The potency of SP600125 towards kinases, including MPS1, JNK, and Aurora kinase A, is determined based on the specific measurement of radioactive phosphotransfer to the substrate. For each enzyme, the absolute Km values for ATP and the specific substrate are initially determined and each assay is then run at optimized [ATP] (2·αKm) and [substrate] (5·Km) concentrations. MPS1 activity is measured using 5 nM of MPS1 recombinant protein in 50 mM HEPES pH 7.5, 2.5 mM MgCl2, 1 mM MnCl2, 1 mM DTT, 3 μM NaVO3, 2 mM β-glycerophosphate, 0.2 mg/mL BSA, 200 μM P38-βtide substrate-peptide (KRQADEEMTGYVATRWYRAE), and 8 μM ATP with 1.5 nM 33P-γ-ATP. Ten serial 1:3 dilutions (from 30 μM to 1.5 nM) of SP600125 are tested and IC50 determined.

    Cell Assay:  Cells ( HCT116, A2780, and U2OS cells) are seeded in 384 well-plates. One day after seeding, the cells are treated with SP600125 for 72 hours and the plates are then processed using a CellTiter-Glo assay. Inhibitory activity is evaluated comparing treated versus control data and IC50 value of proliferation is calculated.

    In VivoIn 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.
    Animal modelMice LPS/TNF model (female CD-1)
    Formulation & DosageDissolved in PPCES (30% PEG-400/20% polypropylene glycol/15% Cremophor EL/5% ethanol/30% saline); 15 or 30mg/kg;  Oral gavage or i.v. injection

    Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13681-6; Cancer Res. 2010 Dec 15;70(24):10255-64.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


    SP600125 attenuates LPS-induced ALI in rats in vivo.  2014 Jul;8(1):153-158


    Effect of SP600125 administration on A549 cell viability and apoptosis.  2014 Jul;8(1):153-158


    Effect of SP600125 in vitro on the expression of claudin-4 and JNK phosphorylation.  2014 Jul;8(1):153-158




    Effect of SP600125 on claudin-4 expression and JNK phosphorylation in vivo.  2014 Jul;8(1):153-158


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