Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Nirogacestat (PF 03084014) 是一种具有口服活性的,可逆的,非竞争性的,选择性γ-secretase 抑制剂,IC50为 6.2 nM。它抑制 Notch 信号通路,可研究 Notch 受体依赖性肿瘤。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 366 | 现货 | ||
5 mg | ¥ 822 | 现货 | ||
10 mg | ¥ 1,370 | 现货 | ||
25 mg | ¥ 2,420 | 现货 | ||
50 mg | ¥ 3,820 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 885 | 现货 |
产品描述 | Nirogacestat (PF 03084014) is a specific γ-secretase inhibitor (IC50: 6.2 nM, in a cell-free assay). |
靶点活性 | γ-secretase (cell-free assay):6.2 nM |
体外活性 | 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%. |
体内活性 | 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%). |
激酶实验 | γ-secretase assay:A DNA fragment encoding amino acids 596 - 695 of the 695-aa isoform of APP (APP695) and the Flag sequence (DYKDDDDK) at the C terminus is generated by PCR amplification with suitably designed oligonucleotides and the APP695 cDNA. The Met that serves as the translation start site is residue 596 of APP695 (the P1 residue with respect to theβ-secretase cleavage site). This DNA fragment is inserted into the prokaryotic expression vector pET2-21b. The recombinant protein, C100Flag, is overproduced in Escherichia coli [strain BL21(DE3)] and purified by Mono-Q column chromatography. C100Flag (1.7 μM) is incubated with cell membranes (0.5 mg/mL) in the presence of CHAPSO, CHAPS (3-[(3-cholamidopropyl)dim-ethylammonio]-1-propanesulfonate), or Triton X-100 (0, 0.125, 0.25, 0.5, or 1%) in buffer B (50 mM Pipes, pH 7.0y 5 mM MgCl2/5 mM CaCl2/150 mM KCl) at 37°C. The reactions are stopped by adding RIPA (150 mM NaCl/1.0% NP-40/0.5% sodium deoxycholate 0.1% SDS/50 mM Tris HCl, pH 8.0) and boiling for 5 min. The samples ae centrifuged and the supernatant solutions are assayed for the Aβ peptides by ECL. The Aβ40- and Aβ42-related products from γ-secretase-mediated processing of C100Flag possess a Met at the N terminus and are thus defined as M-Aβ40 and M-Aβ42, respectively. Likewise, supernatant solution (0.125 mg/mL) from CHAPSO-extracted HeLa cell membranes (solubilized γ-secretase) is incubated with C100Flag (1.7 μM) in buffer B containing 0.25% CHAPSO and subsequently assayed for M-Aβ40 and M-Aβ42 by using ECL. |
细胞实验 | 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. |
动物实验 | 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. |
别名 | PF-03084014, PF-3084014, PF03084014, PF 03084014 |
分子量 | 489.64 |
分子式 | C27H41F2N5O |
CAS No. | 1290543-63-3 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 90 mg/mL (183.8 mM)
H2O: < 1 mg/mL (insoluble or slightly soluble)
Ethanol: 90 mg/mL (183.8 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO / Ethanol | 1 mM | 2.0423 mL | 10.2116 mL | 20.4232 mL | 51.0579 mL |
5 mM | 0.4085 mL | 2.0423 mL | 4.0846 mL | 10.2116 mL | |
10 mM | 0.2042 mL | 1.0212 mL | 2.0423 mL | 5.1058 mL | |
20 mM | 0.1021 mL | 0.5106 mL | 1.0212 mL | 2.5529 mL | |
50 mM | 0.0408 mL | 0.2042 mL | 0.4085 mL | 1.0212 mL | |
100 mM | 0.0204 mL | 0.1021 mL | 0.2042 mL | 0.5106 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。
Nirogacestat 1290543-63-3 Apoptosis Neuroscience Proteases/Proteasome Stem Cells Gamma-secretase PF-03084014 γ-secretase PF-3084014 Gamma secretase cancer inhibit gastrointestinal toxicity PF3084014 Inhibitor Notch PF 3084014 PF03084014 PF 03084014 inhibitor