化合物TAE226 T1918

Product Introduction
Bioactivity


英文名: NVP-TAE 226

描述: NVP-TAE 226 (TAE226) 是一种具有 ATP 竞争性的双重FAK 和IGF-1R 抑制剂，IC50分别为 5.5 nM、140 nM。它还抑制Pyk2、胰岛素受体，IC50分为 3.5 nM、40 nM。

细胞实验: Cell cultures are harvested with 0.05% trypsin and seeded in triplicate at 2 × 104 in 24-well culture plates for 24 h before drug treatment. Culture medium is used for mock treatment. Cells are harvested at the indicated day after treatment, and viable cells are counted using the Vi-cell viability analyze(Only for Reference)

激酶实验: Kinase assay: Kinase activities are assayed in Buffer A or C at 30°C, at a final ATP concentration of 15 μM. Blank values are subtracted and activities calculated as pmoles of phosphate incorporated during a 10 min incubation. Controls are performed with appropriate dilutions of dimethylsulfoxide. In a few cases phosphorylation of the substrate is assessed by autoradiography after SDS-PAGE. GSK-3α/β is purified from porcine brain by affinity chromatography on immobilized axin. It is assayed, following a 1/100 dilution in 1 mg BSA/ml 10 mM DTT, with 5 μl 40 μM GS-1 peptide, a specific GSK-3 substrate, (YRRAAVPPSPSLSRHSSPHQSpEDEEE), in buffer A, in the presence of 15 μM [γ-32P] ATP (3,000 Ci/mmol; 1 mCi/ml) in a final volume of 30 μl. After 30 min incubation at 30°C, 25 μl aliquots of supernatant are spotted onto 2.5 × 3 cm pieces of Whatman P81 phosphocellulose paper, and 20 seconds later, the filters are washed five times (for at least 5 min each time) in a solution of 10 ml phosphoric acid/liter of water. The wet filters are counted in the presence of 1 ml ACS scintillation fluid.

体外活性: 在体内模型中,NVP-TAE226（100 mg/kg,p.o.）对MIA PaCa-2人胰腺肿瘤生长具有显著抑制效果,但不影响体重.在体内模型中,NVP-TAE226剂量依赖性地抑制4T1小鼠乳腺瘤生长和肺转移,这与Y397上FAK的自磷酸化和丝氨酸473上Akt磷酸化的抑制相关.NVP-TAE226（75 mg/kg）使负荷颅内胶质瘤异种移植小鼠的存活率显著增加.在人结肠癌SCID小鼠模型中,NVP-TAE226（100 mg/kg,p.o.）使微血管密度显著降低.

体内活性: NVP-TAE226（0.1-10 μM）对HMEC1细胞的微管形成具有抑制作用。在血清饥饿的U87细胞中,NVP-TAE226（<1 μM）抑制细胞外基质诱导的FAK(Tyr397)自身磷酸化。在U87和U251细胞中,NVP-TAE226（<1 μM）也会抑制IGF-I-诱导的IGF-1R磷酸化及其下游靶点基因活性（如MAPK 和Akt）。在体外胶质瘤细胞系人工基底膜侵袭实验中,与对照组相比, NVP-TAE226（1 μM）对肿瘤细胞侵袭具有抑制效果（>50%）。在caspase-3/7活化和poly(ADP-ribose)聚合酶裂解以及膜联蛋白V凋亡试验中,NVP-TAE226（1 μM）对胶质瘤细胞系,包括野生型p53,仅表现出G(2)-M期阻滞,但负荷突变体p53的胶质瘤细胞则会出现细胞凋亡。在人成神经细胞瘤细胞系SK-N-AS中, NVP-TAE226（5 μM）抑制FAK磷酸化。在人成神经细胞瘤细胞系SK-N-AS中,NVP-TAE226（<10 μM）的治疗会使细胞活性降低,细胞周期阻滞,以及细胞凋亡增加。在U87和U251细胞中,NVP-TAE226（<10 μM）阻碍肿瘤细胞生长,并减弱G(2)-M细胞周期进程,这与细胞周期素B1和磷酸化cdc2(Tyr15)蛋白质表达的减少相关。

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 87 mg/mL (185.5 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
H2O : < 1 mg/mL (insoluble or slightly soluble)


关键字: inhibit | TAE 226 | TAE-226 | IGF-1R | Focal adhesion kinase | Insulin Receptor | NVP-TAE-226 | Inhibitor | Apoptosis | NVP-TAE226 | PTK2 protein tyrosine kinase 2 | Pyk2 | NVP-TAE 226 | NVPTAE 226 | Proline-rich tyrosine kinase 2 | NVP TAE 226 | PTK2 | FAK

相关产品: PD168393 | Selonsertib | Lupeol | Caerin 1.1 TFA | Asperosaponin VI | PATULIN | PRIMA-1 | Hydroxyurea | Ziyuglycoside I | Tetrac

相关库: Angiogenesis related Compound Library | Anti-Cancer Compound Library | Membrane Protein-targeted Compound Library | Kinase Inhibitor Library | Inhibitor Library | Tyrosine Kinase Inhibitor Library | Anti-Cancer Active Compound Library | Apoptosis Compound Library | NO PAINS Compound Library | Anti-Cardiovascular Disease Compound Library

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注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途