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280744-09-4 分子结构
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3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-2,5-dihydro-1H-pyrrole-2,5-dione

ChemBase编号:72492
分子式:C19H12Cl2N2O2
平均质量:371.21678
单一同位素质量:370.02758299
SMILES和InChIs

SMILES:
c1cccc2c1n(cc2C1=C(C(=O)NC1=O)c1ccc(cc1Cl)Cl)C
Canonical SMILES:
Clc1ccc(c(c1)Cl)C1=C(C(=O)NC1=O)c1cn(c2c1cccc2)C
InChI:
InChI=1S/C19H12Cl2N2O2/c1-23-9-13(11-4-2-3-5-15(11)23)17-16(18(24)22-19(17)25)12-7-6-10(20)8-14(12)21/h2-9H,1H3,(H,22,24,25)
InChIKey:
JCSGFHVFHSKIJH-UHFFFAOYSA-N

引用这个纪录

CBID:72492 http://www.chembase.cn/molecule-72492.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-2,5-dihydro-1H-pyrrole-2,5-dione
IUPAC传统名
3-(2,4-dichlorophenyl)-4-(1-methylindol-3-yl)-1H-pyrrole-2,5-dione
别名
SB 216763
3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
SB 216763
CAS号
280744-09-4
MDL号
MFCD09753369
PubChem SID
162037417
24278616
PubChem CID
176158

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID
PubChem 176158 external link

理论计算性质

理论计算性质

JChem
Acid pKa 9.213538  质子受体
质子供体 LogD (pH = 5.5) 4.230717 
LogD (pH = 7.4) 4.224255  Log P 4.2308 
摩尔折射率 97.8484 cm3 极化性 38.437584 Å3
极化表面积 51.1 Å2 可自由旋转的化学键
里宾斯基五规则 true 

分子性质

分子性质

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
DMSO expand 查看数据来源
DMSO: soluble20 mg/mL expand 查看数据来源
H2O: insoluble expand 查看数据来源
外观
orange expand 查看数据来源
熔点
287-288.6 °C(lit.) expand 查看数据来源
保存条件
-20°C expand 查看数据来源
欧盟危险性物质标志
刺激性(Irritant) 刺激性(Irritant) (Xi) expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
德国WGK号
3 expand 查看数据来源
危险公开号
36/37/38 expand 查看数据来源
安全公开号
26-36 expand 查看数据来源
GHS危险品标识
GHS07 expand 查看数据来源
GHS警示词
Warning expand 查看数据来源
GHS危险声明
H315-H319-H335 expand 查看数据来源
GHS警示性声明
P261-P305 + P351 + P338 expand 查看数据来源
个人保护装置
dust mask type N95 (US), Eyeshields, Gloves expand 查看数据来源
保存温度
-20°C expand 查看数据来源
作用靶点
GSK-3 expand 查看数据来源
相关基因信息
human ... GSK3A(2931), GSK3B(2932) expand 查看数据来源
纯度
>98% (HPLC) expand 查看数据来源
95+% expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
Empirical Formula (Hill Notation)
C19H12N2O2Cl2 expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich
Selleck Chemicals -  S1075 external link
Research Area
Description Cancer
Biological Activity
Description SB 216763 is a potent and selective GSK-3α inhibitor with IC50 of 34.3 nM.
Targets GSK-3α
IC50 34.3 nM [1]
In Vitro SB 216763 displays similar potency for GSK-3β with 96% inhibition at 10 μM while exhibiting minimal activity against 24 other protein kinases including PKBα and PDK1 with IC50 of >10 μM. SB 216763 stimulates glycogen synthesis in human liver cells with EC50 of 3.6 μM, and induces dose-dependent transcription of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells with a maximum 2.5-fold induction at 5 μM. [1] SB 216763 protects the cerebellar granule neurones from apoptotic cell death induced by LY-294002 or potassium-deprivation in a concentration-dependent manner, with a maximal neuroprotection at 3 μM in contrast with the effect of lithium chloride at which 10 mM is required. SB 216763 at 3 μM also completely prevents death of chicken dorsal root ganglion sensory neurones induced by LY-294002 regardless of NGF. SB 216763 treatment at 5 μM markedly inhibits the GSK-3-dependent phosphorylation of neuronal-specific microtubule-associated protein tau in cerebellar granule neurones or recombinant tau in HEK293 cells, and induces increased levels of cytoplasmic β-catenin in both cells mimicking the effect of Wnt-mediated inhibition of GSK-3. [2] In pancreatic cancer cell lines including BXPC-3, MIA-PaCa2, PANC1, ASPC1, and CFPAC, SB 216763 treatment at 25-50 μM reduces cell viability in a dose-dependent manner, and leads to significant increase in apoptosis by 50% at 72 hours due to the specific down regulation of GSK-3β, while has no effect in HMEC or WI38 cell lines. [3]
In Vivo Administration of SB 216763 at 20 mg/kg significantly prevents lung inflammation and the subsequent fibrosis in bleomycin (BLM)-induced pulmonary inflammation and fibrosis model in mice by significantly blocking the production of inflammatory cytokines MCP-1 and TNF-α by macrophages, and significantly improves the survival of BLM-treated mice. SB 216763 treatment causes a significant reduction in BLM-induced alveolitis by inhibiting alveolar epithelial cell damage. [4]
Clinical Trials
Features
Protocol
Kinase Assay [1]
GSK-3 activity assay GSK-3 kinase activity is measured, in the presence of various concentrations of SB 216763, in a reaction mixture containing final concentrations of 1 nM human GSK-3α, 50 mM MOPS pH 7.0, 0.2 mM EDTA, 10 mM Mg-acetate, 7.5 mM β-mercaptoethanol, 5% (w/v) glycerol, 0.01% (w/v) Tween-20, 10% (v/v) DMSO, and 28 μM GS-2 peptide substrate. The GS-2 peptide sequence corresponds to a region of glycogen synthase that is phosphorylated by GSK-3. The assay is initiated by the addition of 0.34 μCi [33P]γ-ATP. The total ATP concentration is 10 μM. Following 30 minutes incubation at room temperature the assay is stopped by the addition of one third assay volume of 2.5% (v/v) H3PO4 containing 21 mM ATP. Samples are spotted onto P30 phosphocellulose mats and washed six times in 0.5% (v/v) H3PO4. The filter mats are sealed into sample bags containing Wallac betaplate scintillation fluid. 33P incorporation into the substrate peptide is determined by counting the mats in a Wallac microbeta scintillation counter.
Cell Assay [3]
Cell Lines BXPC-3, MIA-PaCa2, PANC1, ASPC1, and CFPAC cells
Concentrations Dissolved in DMSO, final concentrations ~50 μM
Incubation Time 24, 48, and 72 hours
Methods Cells are exposed to various concentrations of SB 216763 for 24, 48 and 72 hours. Relative cell viability is measured using the MTS assay. Apoptotic cells are determined by staining with Hoechst.
Animal Study [4]
Animal Models C57BL/6N mice with lung inflammation and fibrosis induced by bleomycin (BLM)
Formulation Dissolved in DMSO, and diluted in saline
Doses 20 mg/kg
Administration Intravenously
References
[1] Coghlan MP, et al. Chem Biol, 2000, 7(10), 793-803.
[2] Cross DA, et al. J Neurochem, 2001, 77(1), 94-102.
[3] Ougolkov AV, et al. Cancer Res, 2005, 65(6), 2076-2081.
[4] Gurrieri C, et al. J Pharmacol Exp Ther, 2010, 332(3), 785-794.
Sigma Aldrich -  S3442 external link
Biochem/physiol Actions
Potent, selective, cell permeable glycogen synthase kinase-3 (GSK-3) inhibitor.
SB 216763 is a potent and selective ATP-competitive inhibitor of the serine/threonine protein kinase glycogen synthase kinase-3 (GSK-3) α and β isozymes.
Legal Information
Sold for research purposes under agreement from Glaxo-Smith-Kline

参考文献

参考文献

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