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SP600125

产品号 S1460 公司名称 Selleck Chemicals
CAS号 129-56-6 公司网站 http://www.selleckchem.com
分子式 C14H8N2O 电 话 (877) 796-6397
分子量 220.22612 传 真 (832) 582-8590
纯 度 电子邮件 sales@selleckchem.com
保 存 -20°C Chembase数据库ID: 1554

产品价格信息

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产品别名

标题
SP600125
IUPAC标准名
14,15-diazatetracyclo[7.6.1.0^{2,7}.0^{13,16}]hexadeca-1(15),2,4,6,9(16),10,12-heptaen-8-one
IUPAC传统名
1,9-pyrazoloanthrone

产品登记号

CAS号 129-56-6

产品性质

作用靶点 JNK
成盐信息 Free Base
溶解度 DMSO
保存条件 -20°C

产品详细信息

详细说明 (English)
Research Area
Description Cancer
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.
Targets JNK1 JNK2 JNK3 Aurora A Flt3 TRKA
IC50 40 nM 40 nM 90 nM [1] 60 nM 90 nM 70 nM [4]
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]
Clinical Trials
Features
Protocol
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
Methods 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)
Doses 15 or 30 mg/kg
Administration Administered via intravenous injection or orally
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.
[3] Schmidt M, et al. EMBO Rep, 2005, 6(9), 866-872.
[4] Colombo R, et al. Cancer Res, 2010, 70(24), 10255-64.
[5] Vaishnav D, et al. Biochem Biophys Res Commun, 2003, 307(4), 855-860.
[6] Kim JA, et al. Oncogene, 2010, 29(11), 1702-1716.