Nirogacestat (PF-03084014, PF-3084014)

Catalog No.S8018

Nirogacestat (PF-03084014, PF-3084014) Chemical Structure

Molecular Weight(MW): 489.64

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

Size Price Stock Quantity  
USD 197 In stock
USD 577 In stock
Bulk Discount
Bulk Inquiry

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

Cited by 1 Publication

2 Customer Reviews

  • 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.

Purity & Quality Control

Choose Selective Gamma-secretase Inhibitors

Biological Activity

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

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]
In vivo 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]

Protocol

Kinase Assay:[3]
+ Expand

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.
Cell Research:[1]
+ Expand
  • Cell lines: Human T-ALL cell lines HPB-ALL
  • Concentrations: ~1 μM
  • Incubation Time: 7 days
  • 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.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Human T-cell acute lymphoblastic leukemia xenografts HPB-ALL
  • Formulation: 0.5% methylcellulose
  • Dosages: 150 mg/kg
  • Administration: p.o. twice daily
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 97 mg/mL warmed (198.1 mM)
Ethanol 97 mg/mL warmed (198.1 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 489.64
Formula

C27H41F2N5O
CAS No. 1290543-63-3
Storage powder
in solvent
Synonyms N/A

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • 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):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

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
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
NCT02338531 Withdrawn Breast Cancer Jules Bordet Institute June 2015 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field
selleck catalog

Gamma-secretase Signaling Pathway Map

Related Gamma-secretase Products0

  • AZD3839 New

    AZD3839 is a potent and selective BACE1 inhibitor with Ki of 26.1 nM, about 14-fold selectivity over BACE2. Phase 1.

  • Xanthohumol New

    Xanthohumol, a prenylated chalcone from hop, inhibits COX-1 and COX-2 activity and shows chemopreventive effects. Phase 1.

  • A-438079 HCl New

    A-438079 HCl is a potent, and selective P2X7 receptor antagonist with pIC50 of 6.9.

  • Avagacestat (BMS-708163)

    Avagacestat (BMS-708163) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. Phase 2.

    Features:Appears to be more “notch sparing” than semagacestat (LY450139).

  • RO4929097

    RO4929097 is a γ secretase inhibitor with IC50 of 4 nM in a cell-free assay, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. Phase 2.

  • Semagacestat (LY450139)

    Semagacestat (LY450139) is a γ-secretase blocker for Aβ42, Aβ40 and Aβ38 with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, also inhibits Notch signaling with IC50 of 14.1 nM in H4 human glioma cell. Phase 3.

    Features:The best characterized γ-secretase inhibitor that has reached the clinic.

  • DAPT (GSI-IX)

    DAPT (GSI-IX) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells.

  • MK-0752

    MK-0752 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 5 nM. Phase 1/2.

    Features:A moderately potent γ-secretase inhibitor.

  • LY411575

    LY411575 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), also inhibits Notch cleavage with IC50 of 0.39 nM in APP or NΔE expressing HEK293 cells.

  • Dibenzazepine (YO-01027)

    Dibenzazepine (YO-01027) is a dipeptidic γ-secretase inhibitor with IC50 of 2.6 nM and 2.9 nM in cell-free assays for APPL and Notch cleavage, respectively.

Tags: buy Nirogacestat (PF-03084014, PF-3084014) | Nirogacestat (PF-03084014, PF-3084014) supplier | purchase Nirogacestat (PF-03084014, PF-3084014) | Nirogacestat (PF-03084014, PF-3084014) cost | Nirogacestat (PF-03084014, PF-3084014) manufacturer | order Nirogacestat (PF-03084014, PF-3084014) | Nirogacestat (PF-03084014, PF-3084014) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID