Nirogacestat (PF-03084014, PF-3084014)


Nirogacestat (PF-03084014, PF-3084014)化学構造


Nirogacestat (PF-03084014, PF-3084014) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Phase 2.

サイズ 価格(税別)  
JPY 32702.00
JPY 95782.00



  • The expression of p-EGFR and NICD was assessed by western blot after treatment for 3 d.

    Cell Prolif, 2018, 51(3):e12424. Nirogacestat (PF-03084014, PF-3084014) purchased from Selleck.

    (F) Tumour tissues were further analysed to detect the efficacy of the inhibitors by IHC staining using p-EGFR and Notch1. (4Fa) Notch1 staining was mostly confined on the cell membrane. (4Fc) After Erlotinib treatment, the Notch1 protein was cleaved and translocated to the nucleus. (4Fb) p-EGFR was overexpressed in the control group. (4Fd) Erlotinib treatment inhibited p-EGFR expression. (4Fe-f) PF-03084014 treatment reduced both Notch1 and p-EGFR expression. (4Fg-h) Synthetic therapy reduced the activation of Notch1 and EGFR pathway. Scale bar = 50 μm. *P < .05, **P < .01, ***P < .001

    Cell Prolif, 2017, doi: 10.1111/cpr.12424. Nirogacestat (PF-03084014, PF-3084014) purchased from Selleck.




製品説明 Nirogacestat (PF-03084014, PF-3084014) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Phase 2.
γ-secretase [1]
(cell-free assay)
6.2 nM

PF-03084014 inhibits Notch receptor cleavage in cellular assays using HPB-ALL cells that harbor mutations in both the heterodimerization and PEST domains in Notch1with IC50 of 13.3 nM. PF-03084014 downregulates Notch target genes Hes-1, and cMyc expression in HPB-ALL cells with IC50 of <1 nM and 10 nM, 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 with IC50s of 30-100 nM. [1] PF-03084014 reduces proliferation of HUVECs with IC50 of 0.5 μM, and decreases the lumen formation with an IC50 value of 50 nM. PF-03084014 (1 μM) has no antiproliferative effect in MX1 cells; however, it inhibits migration by 95%. [2]

体内試験 PF-03084014 orally administrated in a single dose of 200 mg/kg, 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 dose of 150 mg/kg, accompanied by a significant reduction of NICD/Notch1, tumor mitotic index (Ki67), and apoptosis (activated caspase-3) staining. [1] PF-03084014 (120 mg/kg) induces apoptosis, antiproliferation, reduces tumor cell self-renewal ability, impaires tumor vasculature, and decreases metastasis activity in breast cancer HCC1599 tumor-bearing mice. PF-03084014 treatment displays significant antitumor activity in various types of the breast xenograft models with TGI value of at least 50%. [2]


+ 展開

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 5mM 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 deoxycholatey 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.
細胞試験: [1]
+ 展開
  • 細胞株: Human T-ALL cell lines HPB-ALL
  • 濃度: ~1 μM
  • 反応時間: 7 days
  • 実験の流れ: 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.
+ 展開
  • 動物モデル: Human T-cell acute lymphoblastic leukemia xenografts HPB-ALL
  • 製剤: 0.5% methylcellulose
  • 投薬量: 150 mg/kg
  • 投与方法: p.o. twice daily

溶解度 (25°C)

体外 DMSO 97 mg/mL (198.1 mM) warming
Ethanol 97 mg/mL warmed (198.1 mM)
Water Insoluble

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。


分子量 489.64


CAS No. 1290543-63-3
in solvent
別名 N/A





質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)


  • 質量





開始濃度 x 開始体積 = 最終濃度 x 最終体積


この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 入力 出力 )

  • C1



  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):




チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2


質量 濃度 体積 分子量


NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02462707 Withdrawn Advanced Solid Tumors Pfizer July 2015 Phase 1
NCT02137564 Withdrawn AIDS-related Kaposi Sarcoma|HIV Infection|Recurrent Kaposi Sarcoma AIDS Malignancy Consortium|National Cancer Institute (NCI)|The EMMES Corporation July 2015 Phase 2
NCT02338531 Withdrawn Breast Cancer Jules Bordet Institute June 2015 Phase 2
NCT02299635 Terminated Triple Negative Breast Neoplasms Pfizer February 2015 Phase 2
NCT02109445 Terminated Metastatic Cancer Pancreas Pfizer|Academic GI Cancer Consortium September 3 2014 Phase 2
NCT01876251 Terminated Breast Cancer Metastatic Pfizer November 2013 Phase 1



Handling Instructions


  • * 必須



Tags: Nirogacestat (PF-03084014, PF-3084014)を買う | Nirogacestat (PF-03084014, PF-3084014) ic50 | Nirogacestat (PF-03084014, PF-3084014)供給者 | Nirogacestat (PF-03084014, PF-3084014)を購入する | Nirogacestat (PF-03084014, PF-3084014)費用 | Nirogacestat (PF-03084014, PF-3084014)生産者 | オーダーNirogacestat (PF-03084014, PF-3084014) | Nirogacestat (PF-03084014, PF-3084014)化学構造 | Nirogacestat (PF-03084014, PF-3084014)分子量 | Nirogacestat (PF-03084014, PF-3084014)代理店
細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID