2. Neuronal Signaling
    Stem Cell/Wnt
    Apoptosis
  3. γ-secretase
    Apoptosis
  4. Nirogacestat

Nirogacestat  (Synonyms: PF-3084014; PF-03084014)

Cat. No.: HY-15185 Purity: 98.76%
COA Handling Instructions

Nirogacestat (PF-3084014) is a reversible, orally bioavailable, noncompetitive, and selective γ-secretase inhibitor with an IC50 of 6.2 nM. Inhibition of Notch signaling by Nirogacestat while minimizing gastrointestinal toxicity presents a promising approach for research of Notch receptor-dependent cancers.

For research use only. We do not sell to patients.

Nirogacestat Chemical Structure

Nirogacestat Chemical Structure

CAS No. : 1290543-63-3

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Free Sample (0.1 - 0.5 mg)   Apply Now  
Solution
10 mM * 1 mL in DMSO USD 109 In-stock
Estimated Time of Arrival: December 31
Solid + Solvent
10 mM * 1 mL
ready for reconstitution
 USD 109 In-stock
Estimated Time of Arrival: December 31
Solid
5 mg USD 99 In-stock
Estimated Time of Arrival: December 31
10 mg USD 165 In-stock
Estimated Time of Arrival: December 31
50 mg USD 660 In-stock
Estimated Time of Arrival: December 31
100 mg USD 1100 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
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Customer Review

Based on 9 publication(s) in Google Scholar

Other Forms of Nirogacestat:

Top Publications Citing Use of Products

    Nirogacestat purchased from MCE. Usage Cited in: Int J Oncol. 2018 Jul;53(1):99-112.  [Abstract]

    The expression of E-cadherin, N-cadherin and Snail in Enza-R cells is examined by western blot analysis. The cells are transfected with Ad-GFP or Ad-HepaCAM for 72 h and treated with 5 μM PF-3084014 for 48 h. GAPDH served as a loading control.

    Nirogacestat purchased from MCE. Usage Cited in: EMBO Mol Med. 2017 Jul;9(7):950-966.  [Abstract]

    Turnover of endogenous CD74 P8 is inhibited by RO4929079 and BMS-906024. Cell lysate Western blot of A20 cells treated with GSIs is developed with In-1 antibody. MK-0752 and Semagacestat tests used the same control lane (0 nM).

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Nirogacestat (PF-3084014) is a reversible, orally bioavailable, noncompetitive, and selective γ-secretase inhibitor with an IC50 of 6.2 nM. Inhibition of Notch signaling by Nirogacestat while minimizing gastrointestinal toxicity presents a promising approach for research of Notch receptor-dependent cancers[1].

    IC50 & Target

    IC50: 6.2 nM (γ-secretase)[1]
    In Vitro

    The IC50 of Nirogacestat (PF-03084014) for γ-secretase enzyme inhibition in cell-free assay for Aβ production using detergent solubilized membranes derived from HeLa cells is determined to be 6.2 nM. When tested for inhibition of Notch receptor cleavage in cellular assays using HPB-ALL cells that harbor mutations in both the heterodimerization and PEST domains in Notch1, the cell IC50 is determined to be 13.3 nM. Nirogacestat (PF-03084014) causes a significant increase in caspase-3 activities in HPB-ALL and TALL-1 cells as well as an induction of cleaved PARP and cleaved caspase-3 after a 7-day treatment[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    In Vivo

    Nirogacestat (PF-03084014) shows robust antitumor activity in this model on 14-day twice daily dosing. Tumor growth inhibition is dose dependent, with maximal tumor growth inhibition of ~92% obtained at high dose levels (150 mg/kg). In tumor growth inhibition studies where mice receive repetitive twice daily dosing for more than a week, Nirogacestat (PF-03084014) is well tolerated at dose levels below 100 mg/kg as no significant weight loss, morbidity, or mortality is observed. When the dose is increased to 150 mg/kg, however, mice have diarrhea and show weight loss (10-15%) approximately 10 days after compound administration. The body weight of treated animals usually returns to normal if dosing holidays are given, suggesting that the toxicity of Nirogacestat (PF-03084014) is reversible[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Clinical Trial
    Molecular Weight

    489.64

    Appearance

    Solid

    Formula

    C27H41F2N5O
    CAS No.
    SMILES

    FC1=C2C(CC[[email protected]](N[[email protected]@H](CCC)C(NC3=CN(C(C)(C)CNCC(C)(C)C)C=N3)=O)C2)=CC(F)=C1
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 6 months
    -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 28.57 mg/mL (58.35 mM; Need ultrasonic)

    H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.0423 mL 10.2116 mL 20.4232 mL
    5 mM 0.4085 mL 2.0423 mL 4.0846 mL
    10 mM 0.2042 mL 1.0212 mL 2.0423 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: 2.5 mg/mL (5.11 mM); Suspended solution; Need ultrasonic and warming

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: 2.5 mg/mL (5.11 mM); Suspended solution; Need ultrasonic

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (5.11 mM); Clear solution

    • 4.

      Add each solvent one by one:  5% DMSO    40% PEG300    5% Tween-80    50% saline

      Solubility: 1.43 mg/mL (2.92 mM); Suspended solution; Need ultrasonic

    *All of the co-solvents are available by MCE.
    Purity & Documentation

    Purity: 98.76%

    COA (248 KB) HNMR (265 KB) CNMR (284 KB) LCMS (256 KB)

    Handling Instructions (2659 KB)
    References
    Cell Assay
    [1]

    Cells are seeded in 96-well plates at 2,000 (Sup-T1, Jurkat, and DND-41) or 10,000 (HPB-ALL or TALL-1) cells/well in growth media supplemented with 10% fetal bovine serum. Serial dilutions of Nirogacestat (PF-03084014) are done in DMSO, appropriate controls or designated concentrations of Nirogacestat (PF-03084014) are added to each well, and cells are incubated at 37°C 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. IC50 values are calculated by using the sigmoidal dose-response (variable slope) in GraphPad Prism[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1][2]

    Mice[1]
    Athymic female mice (nu/nu, 6-8 weeks) are used. For antitumor efficacy, animals bearing tumors of 150 to 300 mm3 in size are randomly divided into groups that received either vehicle (0.5% methylcellulose) or Nirogacestat (PF-03084014) (150 mg/kg, diluted in vehicle), and dosed by oral gavage. Animal body weight and tumor measurements are obtained every 2 to 3 days. Tumor volume (mm3) is measured with Vernier calipers and calculated. Percent (%) inhibition values are measured on the final day of study for drug-treated compared with vehicle-treated mice and are calculated. For all tumor growth inhibition experiments, 8 to 10 mice per dose group are used. Student's t test is used to determine the P value.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    References
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    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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    Keywords:

    Nirogacestat1290543-63-3PF-3084014 PF-03084014PF3084014PF 3084014PF03084014PF 03084014PF-03084014γ-secretaseApoptosisGamma secretaseNotchgastrointestinaltoxicitycancerInhibitorinhibitorinhibit

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