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• 产品描述： GNE-317, a PI3K/mTOR inhibitor, can pass through the blood-brain barrier (BBB).

• 靶点： mTOR;PI3K;PI3K; mTOR

• 体外研究：
  GNE-317, an oxetane derivative synthesized by GDC-0980, is aimed at reducing substrate affinity for efflux transporters. In vitro, GDC-0980 demonstrate similar profiles with GNE-317 in MTS cytotoxicity experiments using the GL261 cell line.

• 体内研究：
  Mice, which are i.c. inoculation with GL261-GFP-Luc cells Seven days later,are treated once daily with the maximum tolerated dose of GDC-0980 (7.5 mg/kg), GNE-317 (30 mg/kg), or vehicle. Tumor growth is tracked in GL261 through bioluminescence imaging on a weekly basis. There are no significant differences in GL261 tumor growth among the 3 groups treated by GDC-0980, GNE-317 or vehicle. The data show that the drugs have limited efficacy in inducing cell death in the GL261 cell line. Although GNE-317 has greater delivery and enhanced therapeutic targeting efficacy, it is not effective in the treatment of the GL261 tumor.

• 细胞实验： Cellular viability assays are set up in a 96-well format with 2000 GL261-GFP-Luc cells plated per well in the culture conditions. GL261, an aggressive C57BL/6J-derived glioma line, is transfected with both green fluorescent protein (GFP) and luciferase (Luc) from separate plasmids.GL261-GFP-Luc cells are cultured in Dulbecco's modified Eagle's medium supplemented with 10% FBS and Penicillin/Streptomycin (100 U/mL) at 5% oxygen, and are selected by 4 mg/mL Puromycin and 4 mg/mL G418. Suspend GNE-317 in DMSO and then diluted with the medium.GL261-GFP-Luc cells are incubated in the presence of drug or vehicle for 48 hours, and viability was assessed by MTS assay. Results were detected using a Synergy Mx automated plate reader,which are set up absorbance at 490 nm and used to determine viability and at 650 nm to account for the background. Numerical values from drug-treated wells are normalized to the values of vehicle-treated wells to yield percent survival.

• 动物实验： 7-week-old C57BL/6J mice are implanted GL261-GFP-Luc cells. When tumors reach 5e7 photons/s/cm2/sr (radiance), mice are orally administered the maximum tolerated the dose,which is defined as <10% drop in mice bodyweight dose, GDC-0980 for 7.5 mg/kg, GNE-317 for 30 mg/kg or vehicle once daily for 3 days. At 1 or 6 hours after the third dose, mice are euthanized with carbon dioxide and perfused with 30 mL PBS.

• 参考文献：
  1. Salphati L, et al. Targeting the PI3K pathway in the brain--efficacy of a PI3K inhibitor optimized to cross the blood-brain barrier. Clin Cancer Res. 2012, 18(22):6239-6248

• 溶解性： soluble  in  DMSO

• 保存条件： -20°C

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.413 ml	12.063 ml	24.127 ml
  5 mM	0.483 ml	2.413 ml	4.825 ml
  10 mM	0.241 ml	1.206 ml	2.413 ml
  50 mM	0.048 ml	0.241 ml	0.483 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *