1. Neuronal Signaling
    Stem Cell/Wnt
    Autophagy
  2. γ-secretase
    Autophagy
  3. DAPT

DAPT (Synonyms: GSI-IX)

Cat. No.: HY-13027 Purity: 99.97%
Handling Instructions

DAPT is a γ-secretase inhibitor with IC50s of 115 and 200 nM for total Aβ and Aβ42, respectively.

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

DAPT Chemical Structure

DAPT Chemical Structure

CAS No. : 208255-80-5

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 74 In-stock
Estimated Time of Arrival: December 31
5 mg USD 67 In-stock
Estimated Time of Arrival: December 31
10 mg USD 115 In-stock
Estimated Time of Arrival: December 31
50 mg USD 355 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Top Publications Citing Use of Products

    DAPT purchased from MCE. Usage Cited in: Department Medicine. Yale University. 2016 Jan.

    Treatment with DAPT does not markedly alter expression of p27Kip1 in bulk or CD133- cells, but dramatically enhances its expression in CD133+ cells.

    DAPT purchased from MCE. Usage Cited in: World J Gastroenterol. 2017 Apr 7;23(13):2330-2336.

    Notch γ-secretase inhibitor attenuates notch and transforming growth factor-β signaling pathways in peripheral blood mononuclear cells of liver fibrosis rats. Western blot analysis of protein expression of Notch1, Hes1, Hes5, TGF-β and Smad3 and quantification in PBMCs (2 × 106) from rats treated with DAPT or DMSO for 24 h.

    DAPT purchased from MCE. Usage Cited in: J Cell Physiol. 2018 Mar;233(3):2225-2237.

    DAPTprevents Nicd splitting from Notch1 and has been recognized as a Notch1 pathway inhibitor. Treatment with DAPT also inhibits the expression of Col IV and FN, resembling the effect of Notch1 siRNA.

    DAPT purchased from MCE. Usage Cited in: Int J Cancer. 2018 Aug 1;143(3):645-656.

    Evaluation of expression change of Notch downstream under the androgen-deprived condition with or without the treatment of DAPT by western blot assay.

    DAPT purchased from MCE. Usage Cited in: Biomed Pharmacother. 2018 Nov;107:1370-1376.

    ECa109 and EC9706 cells are treated with concentrations of GSI-DAPT (0, 10 and 20 μM) for 48 h. The expressions of Notch3, DTX1 and Hes1 are investigated by Western blotting.

    DAPT purchased from MCE. Usage Cited in: Biomed Pharmacother. 2018 Nov;107:1370-1376.

    ECa109 and EC9706 cells are treated with concentrations of GSI-DAPT (0, 10 and 20 μM) for 48 h. The expressions of LSD1 and H3K4me2 are investigated by Western blotting.

    DAPT purchased from MCE. Usage Cited in: J Cell Biochem. 2018 Oct 26. 

    The distribution of aggrecan is increased in the DAPT group.

    DAPT purchased from MCE. Usage Cited in: PLoS One. 2018 Feb 15;13(2):e0193037.

    After DAPT treatment, the protein levels of Notch, Hes1 and Hes5 are downregulated in severe injury group. After DAPT treatment, the protein levels of Bcl-2 are upregulated while those of Bax, caspase-3 and caspase-9 are downregulated.

    DAPT purchased from MCE. Usage Cited in: Drug Des Devel Ther. 2018 Nov 8;12:3847-3854.

    Western anslysis of protein analysis of NOX2, NICD, Hes1, Hes5 in the treatment of TBI, TBI+vehicle, TBI+DAPT and TBI+DPI, respectively.

    DAPT purchased from MCE. Usage Cited in: Neural Regen Res. 2019 Mar;14(3):452-461.

    Western blot assay for Hes1 (left) and Hes5 (right) protein expression in the right prefrontal cortex of cerebral I/R mice following DAPT treatment.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    DAPT is a γ-secretase inhibitor with IC50s of 115 and 200 nM for total Aβ and Aβ42, respectively.

    IC50 & Target

    IC50: 115 nM (Aβ), 200 nM (Aβ42)[5]

    In Vitro

    DAPT inhibits Aβ production over 90%, effects only a modest reduction in APPβ in the culture media. Although APPβ is reduced by about 30% by DAPT treatment, this effect is not concentration-dependent and is reversed by the removal of DAPT[1]. CNE-2 cells are treated with increasing concentrations of DAPT (0, 25, 50 and 75 μM), and the γ-secretase-generated Notch 1 fragment Val1744-NICD is decreased after 48 h in a dose-dependent manner (P<0.01). The activation of γ-secretase is almost completely inhibited by DAPT at the concentration of 50 μM[2].

    In Vivo

    DAPT is administered to PDAPP mice (100 mg/kg s.c.) and the levels of DAPT and Aβ are examined in the brain cortex. Peak DAPT levels of 490 ng/g are achieved in the brain 3 h after treatment, and levels greater than 100 ng/g (~200 nM) are sustained throughout the first 18 h. These brain concentrations of DAPT are in excess of its IC50 for lowering Aβ in neuronal cultures (115 nM), and results in a robust and sustains pharmacodynamic effect[1]. DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and Nuclear factor kappa B in rats. Western blot analyses also show a significant decrease of Notch 1 and NF-κB expression in DAPT (0.03 mg/kg) group (P<0.05 vs. MCAO group)[3].

    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 : 62.5 mg/mL (144.52 mM; Need ultrasonic)

    H2O : < 0.1 mg/mL (insoluble)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.3124 mL 11.5618 mL 23.1235 mL
    5 mM 0.4625 mL 2.3124 mL 4.6247 mL
    10 mM 0.2312 mL 1.1562 mL 2.3124 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

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

      Solubility: 2.08 mg/mL (4.81 mM); Suspended solution; Need ultrasonic

    • 2.

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

      Solubility: 2.08 mg/mL (4.81 mM); Suspended solution; Need ultrasonic

    • 3.

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

      Solubility: ≥ 2.08 mg/mL (4.81 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Cell Assay
    [1]

    Human embryonic kidney cells, transfected with the gene for APP751 (HEK 293) are used for routine Aβ reduction assays. Cells are plated in 96-well plates and allowed to adhere overnight in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum. Cells are pre-treated for 2 h at 37°C with DAPT (0, 0.4, 2, 10, 50 and 250 nM), media are aspirated off and fresh compound solutions applied. After an additional 2-h treatment period, conditioned media are drawn off and analyzed by a sandwich ELISA (266-3D6) specific for total Aβ. Reduction of Aβ production is measured relative to control cells treated with 0.1% DMSO and expressed as a percentage inhibition. Data from at least six doses in duplicate are fitted to a four-parameter logistical model using XLfit software in order to determine potency[1].

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

    Animal Administration
    [1][3]

    Mice[1]
    The three- to four-month-old heterozygous PDAPP transgenic mice overexpressing the APPV717F mutant form of the amyloid precursor protein. Each treatment group (n=10) consists of equal numbers of age-matched male and female animals that are fasted overnight prior to treatment. Both treatment and control groups are dosed at a volume of 10 mL/kg with DAPT or vehicle alone. Tissues are processed and all Aβ and APP measurements are made. After removal of the brain, the cortex from one hemisphere is homogenized, extracted with 5 M guanidine, 50 mM Tris-pH 8.0, centrifuged, and the supernatant is used for Aβ measurements. Cortex from the other hemisphere is snap frozen for analysis of compound levels. Aβ levels are expressed as ng/g of wet tissue weight, and percentage reductions are calculated relative to the mean Aβ level of tissue from vehicle-treated control animals. Data are analyzed with Mann-Whitney non-parametric statistics to assess significance.
    Rats[3]
    Male Sprague-Dawley rats (260-290 g) are used. DAPT solution is stereotactically injected into the lateral cerebral ventricle (LV) immediately after MCAO. The stereotactic injections into the LVs are performed at coordinates −0.8 mm anteroposterior, ±1.5 mm mediolateral and −4.5 mm dorsoventral from the bregma. 30 rats are randomly assigned to three operating groups (10 rats in each group): sham-operated group that receive equal volume of PBS without MCAO operation; MCAO group that receive equal volume PBS after MCAO (MCAO); and DAPT group that receive DAPT as 0.03 mg/kg after MCAO. 24 h after operation the first neurological function is assessed and then 48 h after operation the second neurological function is assessed. Meanwhile, brain water content and infarction volume are measured and compared among different groups.

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

    References
    Molecular Weight

    432.46

    Formula

    C₂₃H₂₆F₂N₂O₄

    CAS No.

    208255-80-5

    SMILES

    FC1=CC(F)=CC(CC(N[[email protected]](C(N[[email protected]](C(OC(C)(C)C)=O)C2=CC=CC=C2)=O)C)=O)=C1

    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 99.97%

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    Cat. No.: HY-13027