Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Crenigacestat (LY3039478) 是一种口服具有活性的Notch 和γ-secretase 的抑制剂,其在多种肿瘤细胞中的IC50为 ∼1nM。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 463 | 现货 | ||
5 mg | ¥ 945 | 现货 | ||
10 mg | ¥ 1,660 | 现货 | ||
25 mg | ¥ 3,320 | 现货 | ||
50 mg | ¥ 4,880 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 997 | 现货 |
产品描述 | Crenigacestat (LY3039478) is an orally bioavailable Notch inhibitor with an IC50 of ~1 nM in most of the tumor cell lines tested. Crenigacestat effectively inhibits mutant Notch receptor activity. In a xenograft tumor model, Crenigacestat inhibited expression of Notch-regulated genes and N1ICD cleavage in the tumor microenvironment. |
靶点活性 | Notch1:1 nM |
体外活性 | LY3039478 is a novel small molecule that is an exquisitely potent inhibitor of Notch-1 intracellular domain (N1ICD) cleavage with an IC50 of ~1 nM in most of the tumor cell lines tested. LY3039478 also potently inhibits mutant Notch receptor activity[2]. Treatment with a gamma secretase inhibitor, LY3039478, significantly inhibited the growth of 2 CCRCC(Clear cell renal cell carcinoma) cell lines in a concentration dependent manner. LY3039478 treatment also led to decreased expression of Myc and Cyclin A1, two genes that were part of the NOTCH driven proliferative signature in murine and human model systems. LY3039478 treatment also led to G0/G1 cell cycle arrest in CCRCC cells[3]. |
体内活性 | In mice, its oral bioavalability(%F) is 65%, clearance(CL)=41 mL/min/kg, VDss = 3.8 L/kg. In Rats, its oral bioavalability(%F) is 65%, CL=98 mL/min/kg, VDss=4.9 L/kg. In Dogs, its oral bioavalability (%F) is 67%, CL=3.8 mL/min/kg, VDss=1.4 L/kg[1]. In a xenograft tumor model, LY3039478 inhibited N1ICD cleavage and expression of Notch-regulated genes in the tumor microenvironment. The inhibition of Notch cleavage also resulted in the induction of apoptosis in a Notch-dependent xenograft model[2]. In immunodeficient NSG mice xenografted with 769-P CCRCC cells, LY3039478 treatment resulted in significantly increased survival and delayed tumor growth in independent cohorts of mice demonstrating in vivo efficacy in CCRCC[3]. |
细胞实验 | K07074 cells were plated to 24-well plates at 10<sup>5</sup> cell/well. Viability of cells was assessed in quadruplicates at indicated timepoints using the CellTiter-Glo luminescent cell viability assay. To study the effect of the small molecular compounds on K07074 cell growth the compounds or DMSO were added to the growth media 24 h after seeding. The cells were incubated with inhibitors and DMSO as indicated. Cell viability was assessed as described above. Each experiment was carried out in triplicate and at least 3 independent experiments were performed. (Only for Reference) |
别名 | LY3039478 |
分子量 | 464.44 |
分子式 | C22H23F3N4O4 |
CAS No. | 1421438-81-4 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 55 mg/mL (118.42 mM)
H2O: < 1 mg/mL (insoluble or slightly soluble)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.1531 mL | 10.7657 mL | 21.5313 mL | 53.8283 mL |
5 mM | 0.4306 mL | 2.1531 mL | 4.3063 mL | 10.7657 mL | |
10 mM | 0.2153 mL | 1.0766 mL | 2.1531 mL | 5.3828 mL | |
20 mM | 0.1077 mL | 0.5383 mL | 1.0766 mL | 2.6914 mL | |
50 mM | 0.0431 mL | 0.2153 mL | 0.4306 mL | 1.0766 mL | |
100 mM | 0.0215 mL | 0.1077 mL | 0.2153 mL | 0.5383 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Crenigacestat 1421438-81-4 Neuroscience Proteases/Proteasome Stem Cells Gamma-secretase Inhibitor γ-secretase LY 3039478 liver LY-3039478 Notch LY3039478 Gamma secretase inhibit CCRCC inhibitor