SP600125

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.

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In DMSO USD 191 In stock
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SP600125 Chemical Structure

SP600125 Chemical Structure
Molecular Weight: 220.23

Validation & Quality Control

Customer Reviews(4)

Quality Control & MSDS

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Product Information

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Product Description

Biological Activity

Description 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.
Targets JNK1 [1] JNK2 [1] Aurora A [4] TrkA [4] JNK3 [1]

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IC50 40 nM 40 nM 60 nM 70 nM 90 nM
In 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] However, later studies reveal that SP600125 also suppresses aryl hydrocarbon receptor (AhR) [2], Mps1 [3], and a panel of other serine/threonine kinases, including Aurora kinase A, FLT3, MELK, and TRKA [4]. In a mouse beta cells MIN6, SP600125 (20 μM) induces the phosphorylation of p38 MAPK and its downstream CREB-dependent promoter activation. [5] 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. [6]
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]
Features

Protocol(Only for Reference)

Kinase Assay: [4]

In Vitro Kinase Assays 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: [4]

Cell lines HCT116, A2780, and U2OS cells
Concentrations 0–5 μM, dissolved in 0.1% DMSO
Incubation Time 72 hours
Method 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.

Animal Study: [1]

Animal Models Mouse LPS/TNF model (female CD-1)
Formulation Dissolved in PPCES (30% PEG-400/20% polypropylene glycol/15% Cremophor EL/5% ethanol/30% saline)
Dosages 15 or 30 mg/kg
Administration Administered via intravenous injection or orally
Solubility 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Bennett BL, et al. Proc Natl Acad Sci U S A, 2001, 98(24), 13681-13686.

[2] Joiakim A, et al. Drug Metab Dispos, 2003, 31(11), 1279-1282.

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Chemical Information

Download SP600125 SDF
Molecular Weight (MW) 220.23
Formula

C14H8N2O

CAS No. 129-56-6
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms Nsc75890
Solubility (25°C) * In vitro DMSO 44 mg/mL (199 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 2H-Dibenzo[cd,g]indazol-6-one

Research Area

Customer Reviews (4)


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Rating
Source Cancer Res 2013 73(20):6346-58. SP600125 purchased from Selleck
Method Immunoblot analysis
Cell Lines MDA-231 cells
Concentrations 10 uM
Incubation Time 24 h
Results cJUN phosphorylation and expression were downregulated by both the SP600125 and selumetinib, with maximal inhibition by the combination.

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Rating
Source Lee lay hoon from National University of Singapore. SP600125 purchased from Selleck
Method ELISA
Cell Lines Bone marrow derived macrophages
Concentrations 10-20 μM
Incubation Time 24 h
Results SP600125 treatment resulted in a reduction of TNF-a production.

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Rating
Source SP600125 purchased from Selleck
Method Sectional Immunohistochemistry
Cell Lines E14.5 male UGSs
Concentrations 10 μM
Incubation Time 4 d
Results Cell elongation index measured from spindle-like morphology was used to d etermine the effect of individual inhibitors. Prevention of MSP-induced spindle-like morphology was not observed in M-RON cells treated with w ortmannin, SB203580, SP600125, Cay10512, and S 31-201, suggesting that signaling from these pathways was not involved in MSP-induced EMT. A moderate effect, based on changes in elongation index, was s een w hen rapa mycin, vismode-gi b, and XAV- 939 were ap plied, suggesti ng that s ignal-ing f rom H edgeho g, Wnt / b -catenin, a nd FRAP /mTOR pathwa ys played a role i n MSP-induced EMT.

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Rating
Source Biochim Biophys Acta, 2012, 1823(5), 987-96. SP600125 purchased from Selleck
Method Immunofluorescence
Cell Lines HC11 cells
Concentrations 50 µM
Incubation Time 1 h
Results whole ADRP levels, estimated by Western blot , decreased only in the presence of MK -2206 and LY294002. In most cases, ADRP decorated the surface of small lipid droplets and appeared as little patches on large cytoplasmic lipid droplets. With the exception of SP600125, which induced a strong ADRP coating of almost all cytoplasmic lipid droplets (although this inhibitor did not increase ADRP synthesis), variation in the distribution of ADRP at the surface of lipid droplet was difficult to estimate, notably because the signal was faint and uneven.

Product Citations (22)

Tech Support & FAQs

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