GNE-317

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

GNE-317  纯度: 99.31%

GNE-317 是一种 PI3K/mTOR 抑制剂,能够穿过血脑屏障 (BBB)。

GNE-317

GNE-317 Chemical Structure

CAS No. : 1394076-92-6

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Free Sample (0.1-0.5 mg)   Apply now  
10 mM * 1 mL in DMSO ¥957 In-stock
5 mg ¥870 In-stock
10 mg ¥1500 In-stock
50 mg ¥4200 In-stock
100 mg ¥5200 In-stock
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生物活性

GNE-317 is a PI3K/mTOR inhibitor, is able to cross the blood-brain barrier (BBB).

IC50 & Target[1]

PI3K

 

mTOR

 

体外研究
(In Vitro)

GNE-317 is an oxetane derivative of GDC-0980 synthesized with the goal of reducing substrate affinity for efflux transporters. In vitro, GDC-0980 and GNE-317 demonstrate similar profiles in MTS cytotoxicity experiments using the GL261 cell line[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

Seven days after i.c. inoculation with GL261-GFP-Luc cells, mice are treated once daily with the maximum tolerated dose of GDC-0980 (7.5 mg/kg), GNE-317 (30 mg/kg), or vehicle. For GL261, tumor growth is tracked through bioluminescence imaging on a weekly basis. There are no significant changes in GL261 tumor growth among the 3 groups. In assessing survival benefits in GL261, neither GDC-0980 nor GNE-317 provides survival benefit over the vehicle-treated animals. The fact that these drugs are not effective in vivo is suggested by the in vitro cytotoxicity data showing that the drugs have limited efficacy in inducing cell death in the GL261 cell line. Neither drug is effective in the GL261 tumor in spite of greater delivery and enhanced therapeutic targeting efficacy of GNE-317[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

分子量

414.48

Formula

C19H22N6O3S

CAS 号

1394076-92-6

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 20 mg/mL (48.25 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.4127 mL 12.0633 mL 24.1266 mL
5 mM 0.4825 mL 2.4127 mL 4.8253 mL
10 mM 0.2413 mL 1.2063 mL 2.4127 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

参考文献
  • [1]. Salphati L, et al. Distribution of the phosphatidylinositol 3-kinase inhibitors Pictilisib (GDC-0941) and GNE-317 in U87 and GS2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging. Drug Metab Dispos. 2014 Jul;42(7):1110-6.

    [2]. Becker CM, et al. Decreased affinity for efflux transporters increases brain penetrance and molecular targeting of a PI3K/mTOR inhibitor in a mouse model of glioblastoma. Neuro Oncol. 2015 Sep;17(9):1210-9.

Cell Assay
[1]

GL261 is an aggressive C57BL/6J-derived glioma line. This cell line is transfected with both green fluorescent protein (GFP) and luciferase (Luc) from separate plasmids. The resultant monoclonal GL261-GFP-Luc cells are maintained in Dulbecco’s modified Eagle’s medium supplemented with 10% FBS and Penicillin/Streptomycin (100 U/mL) and cultured at 5% oxygen. Cell selection used 4 mg/mL Puromycin and 4 mg/mL G418. Cellular viability assays are set up in a 96-well format with 2000 cells plated per well in the culture conditions. Cells are incubated in the presence of drug or vehicle for 48 hours, and viability was assessed by MTS assay. Absorbance at 490 nm is used to determine viability and at 650 nm to account for background using a Synergy Mx automated plate reader. Numerical values from drug-treated wells are normalized to the values of vehicle-treated wells to yield percent survival[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Mice[1]
GL261-GFP-Luc cells are implanted into 7-week-old C57BL/6J mice. When tumors reach 5e7 photons/s/cm2/sr (radiance), animals are orally administered the maximum tolerated dose of GDC-0980 (7.5 mg/kg), GNE-317 (30 mg/kg) or vehicle once a day for 3 days. The maximum tolerated doses are defined as the greatest dose that could be administered to mice with <10% drop in bodyweight. Even at these different doses, both doses provide similar plasma concentrations and thus the same overall systemic exposure. At 1 or 6 hours after the third dose, mice are euthanized with carbon dioxide and perfused with 30 mL PBS. With the aid of GFP goggles, brains are dissected into tumor core, tumor rim, and normal brain tissue. Tissue samples and blood are processed, and tissue specimens from each group are analyzed for drug concentrations using LC-MS/MS.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Salphati L, et al. Distribution of the phosphatidylinositol 3-kinase inhibitors Pictilisib (GDC-0941) and GNE-317 in U87 and GS2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging. Drug Metab Dispos. 2014 Jul;42(7):1110-6.

    [2]. Becker CM, et al. Decreased affinity for efflux transporters increases brain penetrance and molecular targeting of a PI3K/mTOR inhibitor in a mouse model of glioblastoma. Neuro Oncol. 2015 Sep;17(9):1210-9.

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