噻尔非尼 T2624

Product Introduction
Bioactivity


英文名: OSI-930

描述: OSI-930 是 Kit，KDR 和 CSF-1R (c-Fms)的口服选择性抑制剂，IC50分别为 80 nM，9 nM 和 15 nM。它具有抗肿瘤活性，靶向肿瘤中的癌细胞增殖和血管生成。它还适度抑制 Flt-1，c-Raf 和 Lck，并且对 PDGFRα/β，Flt-3和 Abl 具有较弱的抑制活性。

细胞实验: For assays of cell proliferation and apoptosis, cells are seeded into 96-well plates and incubated for 2 to 3 days in the presence of OSI-930 at various concentrations. Inhibition of cell growth is determined by luminescent quantitation of the intracellular ATP content using CellTiterGlo. Induction of caspase-dependent apoptosis by OSI-930 is quantitated by an enzymatic caspase 3/7 assay. Inhibition of angiogenesis by OSI-930 is monitored using the rat aortic ring endothelial sprout outgrowth assay. Sections of aorta are prepared from CO2-euthanized male rats and cultured in vitro in a collagen matrix in the presence or absence of OSI-930. The collagen matrix is prepared from type 1 rat tail collagen solubilized in 0.1% acetic acid at 3 mg/mL, which is combined with 0.125 volume collagen buffer (0.05 N NaOH, 200 mM HEPES, 260 mM NaHCO3), 0.125 volume of medium 199, 0.0125 volume of 1 M NaOH, and 1% GlutaMax. Aortic rings are embedded in 0.4 mL of this matrix in six-well plates, to which 0.5 mL endothelial basal medium and the appropriate amount of OSI-930 is added; the rings are then incubated for 10 days and the resultant angiogenic sprout outgrowth is digitally quantitated from images by measurement of the sprout-containing area within a series of concentric rings around the aortic tissue area.(Only for Reference)

激酶实验: Protein kinase assays : Protein kinase assays are either done in-house by ELISA-based assay methods (Kit, KDR, PDGFRα, and PDGFRβ) or by a radiometric method. In-house ELISA assays used poly(Glu:Tyr) as the substrate bound to the surface of 96-well assay plates; phosphorylation is then detected using an antiphosphotyrosine antibody conjugated to HRP. The bound antibody is then quantitated using ABTS as the peroxidase substrate by measuring the absorbance at 405/490 nm. All assays uses purified recombinant kinase catalytic domains that are either expressed in insect cells or in bacteria. The Kit and EGFR protein used for in-house assays are prepared internally; other enzymes are obtained. Recombinant Kit protein is expressed as an NH2-terminal glutathione S-transferase fusion protein in insect cells and is initially purified as a nonphosphorylated (nonactivated) enzyme with a relatively high Km for ATP (400 μM). In some assays, an activated (tyrosine phosphorylated) form of the enzyme is prepared by incubation with 1 mM ATP for 1 hour at 30 °C. The phosphorylated protein is then passed through a desalting column to remove the majority of the ATP and stored at ?80 °C in buffer containing 50% glycerol. The resultant preparation has a considerably higher specific activity and a lower Km for ATP (25 μM) than the initial nonphosphorylated preparation. The inhibition of Kit autophosphorylation by OSI-930 is assayed by incubation of the nonphosphorylated enzyme at 30 °C in the presence of 200 μM ATP and various concentrations of OSI-930. The reaction is stopped by removal of aliquots into SDS-PAGE sample buffer followed by heating to 100 °C for 5 minutes. The degree of phosphorylation of Kit is then determined by immunoblotting for both total Kit and phosphorylated Kit.

体外活性: 在HMC-1, NCI-SNU-5, COLO-205和U251移植瘤模型中,口服OSI-930（200 mg/kg）能够够抑制肿瘤细胞增殖.

体内活性: 在HMC-1 细胞系中（IC50=14 nM）,OSI-930抑制细胞增殖,诱导细胞凋亡。OSI-930能够抑制多种重组受体酪氨酸激酶,Kit（IC50=80 nM）, KDR（IC50=9 nM）, Flt（ IC50=8 nM）, CSF-1R（IC50=15 nM）, c-Raf （IC50=41 nM）和Lck（IC50=22 nM）。

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

溶解度: DMSO : 82 mg/mL (184.9 mM)
Ethanol : 3 mg/mL (6.76 mM)


关键字: CSF-1R | Inhibitor | CD117 | Vascular endothelial growth factor receptor | CSF1R | colony stimulating factor 1 receptor | antitumor | c-Fms | SCFR | c-Kit | VEGFR | selective | OSI930 | CSF-1 receptor | OSI-930 | Apoptosis | inhibit

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相关库: Drug Repurposing Compound Library | Anti-Cancer Compound Library | Anti-Cancer Drug Library | Clinical Compound Library | Membrane Protein-targeted Compound Library | Kinase Inhibitor Library | Inhibitor Library | Anti-Cancer Clinical Compound Library | Tyrosine Kinase Inhibitor Library | Anti-Cancer Active 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