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• 產品描述： PF-03084014 (PF-3084014) is a specific γ-secretase inhibitor (IC50: 6.2 nM, in a cell-free assay).

• 靶點： Apoptosis;Gamma-secretase;Apoptosis;?Gamma-secretase

• 體外研究：
  PF-03084014 inhibits Notch receptor cleavage in HPB-ALL cells that harbor mutations in both the heterodimerization and PEST domains in Notch1 (IC50: 13.3 nM). PF-03084014 downregulates Notch target genes Hes-1 (IC50<1 nM) and cMyc expression (IC50:10 nM) in HPB-ALL cells, respectively. PF-03084014 inhibits cell growth of a subset of human T-ALL cell lines (HPB-ALL, DND-41, TALL-1, and Sup-T1) through induction of cell cycle arrest and apoptosis (IC50s: 30-100 nM). PF-03084014 reduces proliferation of HUVECs (IC50: 0.5 μM) and decreases the lumen formation (IC50: 50 nM). PF-03084014 (1 μM) has no antiproliferative effect in MX1 cells; however, it inhibits migration by 95%.

• 體內研究：
  PF-03084014 (200 mg/kg, p.o.) causes maximal NICD inhibition for ～80% in xenograft HPB-ALL tumors. PF-03084014 shows robust antitumor activity in this mode with a maximal tumor growth inhibition of 92% at the dose of 150 mg/kg, accompanied by a significant reduction of NICD/Notch1, tumor mitotic index (Ki67), and apoptosis (activated caspase-3) staining. PF-03084014 (120 mg/kg) induces apoptosis, antiproliferation, reduces tumor cell self-renewal ability, impairs tumor vasculature, and decreases metastasis activity in breast cancer HCC1599 tumor-bearing mice. In various types of the breast xenograft models, PF-03084014 has significant antitumor activity (TGI>50%).

• 細胞實驗： Cell lines: Human T-ALL cell lines HPB-ALL. Concentrations: ~1 μM. Method: Cells are seeded in 96-well plates at 10,000 cells/well in growth media supplemented with 10% fetal bovine serum.Serial dilutions of PF-03084014 are done in DMSO,appropriate controls or designated concentrations of PF-03084014 are added to each well,and cells are incubated at 37℃ for 7 days (final DMSO content 0.1%).Resazurin at a final concentration of 0.1 mg/mL is added to the cells and plates are incubated for 2 to 4 hours.Fluorescent signals are read as emission at 590 nm after excitation at 560 nm.

• 動物實驗： Animal Models: Human T-cell acute lymphoblastic leukemia xenografts HPB-ALL. Formulation: 0.5% methylcellulose. Dosages: 150 mg/kg,b.i.d. Administration: p.o.

• 參考文獻：
  1. Wei P, et al. Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design. Mol Cancer Ther. 2010 Jun;9(6):1618-28. 2. Zhang CC, et al. Biomarker and pharmacologic evaluation of the γ-secretase inhibitor PF-03084014 in breast cancer models. Clin Cancer Res, 2012, 18(18), 52008-52019. 3. Li YM, et al. Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state. Proc Natl Acad Sci USA, 2000, 97(11), 6138-6143.

• 溶解性： Soluble  in  DMSO、Ethanol

• 保存條件： -20℃

• 配置溶液濃度參考：
  

  	1mg	5mg	10mg
  1 mM	2.042 ml	10.212 ml	20.423 ml
  5 mM	0.408 ml	2.042 ml	4.085 ml
  10 mM	0.204 ml	1.021 ml	2.042 ml
  50 mM	0.041 ml	0.204 ml	0.408 ml

• 注意：部分產品我司僅能提供部分信息，我司不保證所提供信息的權威性，僅供客戶參考交流研究之用。

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本計算器可幫助您計算出特定溶液中溶質的質量、溶液濃度和體積之間的關系，公式為：

質量 (mg) = 濃度 (mM) x 體積 (mL) x 分子摩爾量 (g/mol)

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