Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Samotolisib (LY3023414) 在低纳摩尔浓度下,有效抑制mTORC1/2。它选择性地有效抑制PI3Kα、PI3Kβ、PI3Kδ、PI3Kγ、DNA-PK 和mTOR,IC50分别为 6.07 nM、77.6 nM、38 nM、23.8 nM、4.24 nM 和 165 nM。它可用于多种肿瘤和癌症的试验。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 413 | 现货 | ||
2 mg | ¥ 588 | 现货 | ||
5 mg | ¥ 980 | 现货 | ||
10 mg | ¥ 1,590 | 现货 | ||
25 mg | ¥ 3,280 | 现货 | ||
50 mg | ¥ 4,790 | 现货 | ||
100 mg | ¥ 6,690 | 现货 | ||
500 mg | ¥ 13,300 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 889 | 现货 |
产品描述 | Samotolisib (LY3023414) is an oral ATP competitive inhibitor of the class I PI3K isoforms, DNA-PK, and mTOR. Samotolisib (LY3023414) has been used in trials studying the treatment of Neoplasm, Solid Tumor, COLON CANCER, BREAST CANCER, and Advanced Cancer, among others. |
靶点活性 | mTOR:165 nM, PI3Kγ:23.8 nM, PI3Kα:6.07 nM, DNA-PK:4.24 nM, PI3Kβ:77.6 nM, PI3Kδ:38 nM |
体外活性 | LY3023414 shows high solubility across a wide pH range. In vitro, inhibition of PI3K/AKT/mTOR signaling by LY3023414 causes G1 cell-cycle arrest and resulted in broad antiproliferative activity in cancer cell panel screens. In cell-based assays, LY3023414 inhibition of PI3K and mTOR is assessed in the PTEN-deficient U87 MG glioblastoma cell line. LY3023414 inhibits the phosphorylation of AKT at position T308 downstream of PI3K at an IC50 of 106 nM. Similarly, LY3023414 inhibits phosphorylation of AKT at position S473 (IC50 = 94.2 nM) by mTORC2 as well as phosphorylation of mTORC1 kinase targets p70S6K (position T389; IC50 =10.6 nM) and 4E-BP1 (positions T37/46; IC50 = 187 nM). The downstream phosphorylation of S6RP at positions pS240/244 (IC50 = 19.1 nM) by p70S6K was inhibited as well, indicating target inhibition along the entire PI3K/AKT/mTOR pathway by LY3023414[1]. |
体内活性 | In vivo, LY3023414 demonstrates high bioavailability and dose-dependent dephosphorylation of PI3K/AKT/mTOR pathway downstream substrates such as AKT, S6K, S6RP, and 4E-BP1 for 4 to 6 hours, reflecting the drug's half-life of 2 hours. Intermittent target inhibition is sufficient for its antitumor activity. LY3023414 shows time- and dose-dependent target inhibition in vivo. It is currently being evaluated in phase 1 and 2 trials for the treatment of human malignancies[1]. |
激酶实验 | Western blot analysis: The phosphorylation status of c-Met and VEGFR-2 is detected by Western blot analysis. For c-Met, MKN45 cells are incubated with a serial dilution of E7050 in complete medium at 37 °C for 2 h. For VEGFR-2, HUVEC are starved with human endothelial serum free medium containing 0.5% FBS for 24 h. Subsequently HUVEC are incubated with a serial dilution of E7050 for 1 h and then incubated with 20 ng/mL of human VEGF for 5 min. Cells are lysed by lysis buffer (50 mM HEPES [pH 7.4], 150 mM NaCl, 10% glycerol, 1% Triton X-100, 1.5 mM MgCl2, 1 mM EDTA [pH 8.0], 100 mM NaF, 1 mM phenylmethylsulfonyl fluoride 1 mM sodium orthovanadate, 10 μg/mL aprotinin, 50 μg/mL leupeptin, and 1 μg/mL pepstatin A). The resected tumor samples are homogenized with lysis buffer containing 25 mM β-glycerophosphate and 0.5% (v/v) phosphatase inhibitor cocktail 2 at 4 °C. Cellular debris is removed by centrifugation at 17 860 g for 20 min at 4 °C. Aliquots of the supernatants containing 5-20 μg of protein are subjected to SDS-PAGE under reducing conditions. The proteins are then transferred onto PVDF membranes, blocked with TBS containing 0.05% Tween-20 and either 5% skim milk or 5% BSA. The membranes are probed with the following antibodies: anti-c-Met polyclonal antibody (C-28) and anti-VEGFR-2 polyclonal antibody (C-20); mouse anti-phosphotyrosine clone 4 g10; and anti-VEGFR-2 polyclonal antibody, anti-phospho-VEGFR-2 (Tyr996) polyclonal antibody, and anti-phospho-c-Met (Tyr1234/1235) polyclonal antibody. Detection is performed using a Super Signal enhanced chemiluminescence kit. Immunoreactive bands are visualized by chemiluminescence with an Image Master-VDS-CL detection system. The intensity of each band is measured by using an image analyzer. |
别名 | GTPL8918, LY3023414 |
分子量 | 406.48 |
分子式 | C23H26N4O3 |
CAS No. | 1386874-06-1 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ethanol: 57 mg/mL (140.2 mM)
DMSO: 44 mg/mL (108.2 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 |
Ethanol / DMSO | 1 mM | 2.4601 mL | 12.3007 mL | 24.6015 mL | 61.5036 mL |
5 mM | 0.492 mL | 2.4601 mL | 4.9203 mL | 12.3007 mL | |
10 mM | 0.246 mL | 1.2301 mL | 2.4601 mL | 6.1504 mL | |
20 mM | 0.123 mL | 0.615 mL | 1.2301 mL | 3.0752 mL | |
50 mM | 0.0492 mL | 0.246 mL | 0.492 mL | 1.2301 mL | |
100 mM | 0.0246 mL | 0.123 mL | 0.246 mL | 0.615 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。
Samotolisib 1386874-06-1 Autophagy DNA Damage/DNA Repair PI3K/Akt/mTOR signaling DNA-PK mTOR PI3K Inhibitor GTPL8918 Phosphoinositide 3-kinase LY3023414 DNA-dependent protein kinase inhibit LY-3023414 GTPL-8918 GTPL 8918 LY 3023414 Mammalian target of Rapamycin inhibitor