(3Z)-N-(3-chlorophenyl)-3-{[3,5-dimethyl-4-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-2-yl]methylidene}-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide

• ChemBase编号: 72497
• 分子式: C28H30ClN5O4S
• 平均质量: 568.0869
• 单一同位素质量: 567.17070315
• SMILES: c1(cccc(c1)N(C)S(=O)(=O)c1cc2c(cc1)NC(=O)/C/2=C\c1[nH]c(c(c1C)C(=O)N1CCN(CC1)C)C)Cl
• Canonical SMILES: CN1CCN(CC1)C(=O)c1c(C)[nH]c(c1C)/C=C/1\C(=O)Nc2c1cc(cc2)S(=O)(=O)N(c1cccc(c1)Cl)C
• InChI: InChI=1S/C28H30ClN5O4S/c1-17-25(30-18(2)26(17)28(36)34-12-10-32(3)11-13-34)16-23-22-15-21(8-9-24(22)31-27(23)35)39(37,38)33(4)20-7-5-6-19(29)14-20/h5-9,14-16,30H,10-13H2,1-4H3,(H,31,35)/b23-16-
• InChIKey: FPYJSJDOHRDAMT-KQWNVCNZSA-N

名称和登记号

名称

• IUPAC标准名: (3Z)-N-(3-chlorophenyl)-3-{[3,5-dimethyl-4-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-2-yl]methylidene}-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide; N-(3-chlorophenyl)-3-{[3,5-dimethyl-4-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-2-yl]methylidene}-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide
• IUPAC传统名: (3Z)-N-(3-chlorophenyl)-3-{[3,5-dimethyl-4-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-2-yl]methylidene}-N-methyl-2-oxo-1H-indole-5-sulfonamide; N-(3-chlorophenyl)-3-{[3,5-dimethyl-4-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-2-yl]methylidene}-N-methyl-2-oxo-1H-indole-5-sulfonamide
• 别名: PKI-SU11274; SU11274(PKI-SU11274); (3Z)-N-(3-Chlorophenyl)-3-({3,5-dimethyl-4-[(4-methylpiperazin-1-yl)carbonyl]-1H-pyrrol-2-yl}methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide; SU 11274

登记号

• CAS号: 658084-23-2
• MDL号: MFCD08276928
• PubChem SID: 24724625; 162037422
• PubChem CID: 9549297

理论计算性质

• Acid pKa: 10.708012
• 质子受体: 5
• 质子供体: 2
• LogD (pH = 5.5): 2.0196705
• LogD (pH = 7.4): 3.3177419
• Log P: 3.438596
• 摩尔折射率: 156.0141 cm^3
• 极化性: 58.48911 Å^3
• 极化表面积: 105.82 Å^2
• 可自由旋转的化学键: 4
• 里宾斯基五规则: false

分子性质

理化性质

• 溶解度: DMSO; DMSO: soluble10 mg/mL at 60 °C; H2O: insoluble
• 外观: orange powder

安全信息

• 保存条件: -20°C
• 欧盟危险性物质标志: 刺激性(Irritant) (Xi)
• 德国WGK号: 3
• 危险公开号: 36/37/38
• 安全公开号: 26-36
• GHS危险品标识: GHS07
• GHS警示词: Warning
• GHS危险声明: H315-H319-H335
• GHS警示性声明: P261-P305 + P351 + P338
• 个人保护装置: dust mask type N95 (US), Eyeshields, Gloves
• 保存温度: 2-8°C

药理学性质

• 作用靶点: c-Met

产品相关信息

• 纯度: ≥98% (HPLC)
• 成盐信息: Free Base
• Empirical Formula (Hill Notation): C28H30ClN5O4S

详细说明

Selleck Chemicals - S1080

Research Area

• Description: Cancer

Biological Activity

• Description: SU11274 is a selective Met inhibitor with IC50 of 10 nM.
• Targets: Met
• IC50: 10 nM ^[1]
• In Vitro: SU11274 exhibits greater than 50-fold selectivity for Met versus Flk and more than 500 times selectivity versus other tyrosine kinases such as FGFR-1, c-src, PDGFbR, and EGFR. SU11274 inhibits the phosphorylation of key regulators of the PI3K pathway, including AKT, FKHR, or GSK3β. SU11274 treatment inhibits the growth of TPR-MET-transformed BaF3 cells in a dose-dependent manner with IC50 of <3 μm="" in="" the="" absence="" of="" interleukin="" 3,="" without="" growth="" inhibition="" of="" baf3="" cells="" transformed="" by="" other="" oncogenic="" tyrosine="" kinases,="" including="" bcr-abl,="" tel-jak2,="" tel-abl,="" and="" tel-pdgfβr.="" in="" addition="" to="" cell="" growth,="" su11274="" treatment="" significantly="" inhibits="" the="" migration="" of="" baf3.="" tpr-met="" cells="" by="" 44.8%="" and="" 80%="" at="" 1="" μm="" and="" 5="" μm,="" respectively.="" su11274="" inhibits="" hgf-dependent="" phosphorylation="" of="" met="" as="" well="" as="" hgf-dependent="" cell="" proliferation="" and="" motility="" with="" an="" ic50="" of="" 1-1.5="" μm.="" in="" h69="" and="" h345="" cells="" which="" have="" functional="" met="" receptor,="" su11274="" inhibits="" the="" hgf-induced="" cell="" growth="" with="" ic50="" of="" 3.4="" μm="" and="" 6.5="" μm,="" respectively.="" su11274="" induces="" g1="" cell="" cycle="" arrest="" with="" cells="" in="" g1="" phase="" increased="" from="" 42.4%="" to="" 70.6%="" at="" 5="" μm,="" and="" induces="" caspase-dependent="" apoptosis="" by="" 24%="" at="" 1="" μm.="">^[2] SU11274 inhibits cell viability in c-Met-expressing non-small cell lung cancer (NSCLC) cells with IC50 values of 0.8-4.4 μM, and abrogates hepatocyte growth factor-induced phosphorylation of c-Met and its downstream signaling. ^[3]

Protocol

• Protocol: Kinase Assay ^[1]
• In vitro Met kinase assay: A chimeric protein is constructed containing the cytoplasmic domain of human c-Met fused to Glutathione S-transferase (GST) and expressed in SF9 cells. The c-Met kinase GST-fusion protein is used for an ELISA-based Met biochemical assay using the random copolymer poly(Glu:Tyr) (4:1) immobilized on microtiter plates as a substrate. IC50 value is determined with various concentrations of SU11274 in a buffer containing 5 μM ATP and 10 mM MnCl₂, 50 mM HEPES (pH 7.5), 25 mM NaCl, 0.01% BSA, and 0.1 mM Na orthovanadate. The kinase reaction is performed for 5 minutes at room temperature. The extent of substrate phosphorylation is measured using horseradish peroxidase-conjugated anti-pTyr antibodies.
• Protocol: Cell Assay ^[2]
• Cell Lines: BaF3.TPR-MET, H69 and H345 cells
• Concentrations: Dissolved in DMSO, final concentrations ~10 μM
• Incubation Time: 24, 48, and 72 hours
• Methods: Cells are exposed to various concentrations of SU11274 in the presence or absence of HGF for 24, 48, and 72 hours. The number of viable cells is determined using the MTT assay or trypan blue exclusion. Cell Cycle and apoptosis are measured by fluorescence-activated cell sorter analysis via propidium iodide staining and Annexin V-positive staining, respectively.

References

• References: [1] Wang X, et al. Mol Cancer Ther, 2003, 2(11):1085-1092.
• References: [2] Sattler M, et al. Cancer Res, 2003, 63(17), 5462-5469.
• References: [3] Ma PC, et al. Cancer Res, 2005, 65(4), 1479-1488.

Sigma Aldrich - S9820

Biochem/physiol Actions
SU 11274 is a Met tyrosine kinase inhibitor.

参考文献

• Wang X, et al. Mol Cancer Ther, 2003, 2(11):1085-1092.
• Ma PC, et al. Cancer Res, 2005, 65(4), 1479-1488.
• Sattler M, et al. Cancer Res, 2003, 63(17), 5462-5469.