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• 产品描述： GDC-0084 (RG7666) is a PI3K inhibitor with potential antineoplastic activity. GDC-0084 specifically inhibits PI3K in the PI3K/AKT kinase (or protein kinase B) signaling pathway, thereby inhibiting the activation of the PI3K signaling pathway. This may result in the inhibition of both cell growth and survival in susceptible tumor cell populations

• 靶点： mTOR;PI3K;PI3K;mTOR

• 体外研究：
  GDC-0084对小鼠脑中的PI3K信号通路有明显抑制效果,可抑制高达90%的pAkt信号.在U87和GS2原位移植瘤模型中,GDC-0084对肿瘤生长分别具有70%和40%的抑制作用.GDC-0084的疗效正处于临床患者检测评估阶段,暴露的耐受剂量与小鼠模型中的有效剂量一致

• 体内研究：
  在人微粒体及干细胞培养中,GDC-0084显示出良好的代谢稳定性,能抑制正常脑组织中PI3K通路的关键信号pAKT。GDC-0084抑制多种神经胶质瘤细胞的增殖（IC50：0.3-1.1 μM）。GDC-0084与血浆蛋白结合率较低,在CD-1小鼠血浆中游离分数为29.5±2.7%（n=3,5 μM）,而在CD-1小鼠中与脑组织结合率较高,游离分数只有6.7±1%(n=3)

• 细胞实验： For transport studies, cells are seeded on 24-well Millicell plates 4 days prior to use(polyethylene terephtalate membrane, 1 μm pore size) at a seeding density of 1.3×105 cells/ml). GDC-0084 is tested at 5 μM in the apical-tobasolateral (A-B) and basolateral-to-apical (B-A) directions. The compound is dissolved in transport buffer consisting of Hanks' balanced salt solution with 10 mM HEPES. Lucifer Yellow is used as the paracellular and monolayer integrity marker. GDC-0084 concentrations in the donor and receiving compartments are determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The apparent permeability (Papp), in the apical to A-B and B-A directions, is calculated after 2-hour incubation.(Only for Reference)

• 参考文献：
  1: Salphati L, Alicke B, Heffron TP, Shahidi-Latham S, Nishimura M, Cao T, Carano RA, Cheong J, Greve J, Koeppen H, Lau S, Lee LB, Nannini-Pepe M, Pang J, Plise EG, Quiason C, Rangell L, Zhang X, Gould SE, Phillips HS, Olivero AG. Brain Distribution and Efficacy of the Brain Penetrant PI3K Inhibitor GDC-0084 in Orthotopic Mouse Models of Human Glioblastoma. Drug Metab Dispos. 2016 Dec;44(12):1881-1889. Epub 2016 Sep 16. PubMed PMID: 27638506.
  
  2: Heffron TP, Ndubaku CO, Salphati L, Alicke B, Cheong J, Drobnick J, Edgar K, Gould SE, Lee LB, Lesnick JD, Lewis C, Nonomiya J, Pang J, Plise EG, Sideris S, Wallin J, Wang L, Zhang X, Olivero AG. Discovery of Clinical Development Candidate GDC-0084, a Brain Penetrant Inhibitor of PI3K and mTOR. ACS Med Chem Lett. 2016 Feb 16;7(4):351-6. doi: 10.1021/acsmedchemlett.6b00005. eCollection 2016 Apr 14. PubMed PMID: 27096040; PubMed Central PMCID: PMC4834666.

• 溶解性： soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.615 ml	13.075 ml	26.149 ml
  5 mM	0.523 ml	2.615 ml	5.23 ml
  10 mM	0.261 ml	1.307 ml	2.615 ml
  50 mM	0.052 ml	0.261 ml	0.523 ml

• 注意：部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。

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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 *