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DAPT

Cat. No. M1746
DAPT Structure
Synonym:

GSI-IX

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10mg USD 100 In stock
50mg USD 300 In stock
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Quality Control
Biological Activity

DAPT (GSI-IX) is a γ-secretase inhibitor with IC50 values of 115 and 200 nM for total Aβ and Aβ42 respectively. DAPT (GSI-IX) may be useful in the study of β-amyloid (Aβ) formation. As an inhibitor of Notch, DAPT may advance studies of autoimmune and lymphoproliferative diseases, such as ALPS and lupus erythematosus (SLE). Other γ-secretase substrates include LDL receptor-related protein, E-cadherin and ErbB-4.

Protocol
Cell Experiment
Cell lines SK-MES-1
Preparation method Cells are seeded into 96-well plates and exposed to 0.1% DMSO or DAPT at concentrations in the range of 2.5 μM–160 μM for 72 hours. Cytotoxicity is determined with 3-(4, 5)-dimethylthiahiazo-(-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) dye reduction assay with minor modifications. Briefly, after incubation with DAPT, 20 μL MTT solution (5 mg/mL in PBS) is added to 180 μL medium in each well and plates are incubated for 4 hours at 37 °C, and subsequently 150 μL DMSO is added to each well, and mixed by shaking at room temperature for 15 minutes. Absorption is measured by an enzyme-linked immunosorbent assay at 490 nm to determine absorbance values.
Concentrations 2.5 ~ 160 μM
Incubation time 72 h
Animal Experiment
Animal models MCAO rat model
Formulation prepared by dissolving DAPT powder in 0.01 M phosphate-buffered saline containing 5% dimethyl sulfoxide (Fisher Scientific, Fair Lawn, NJ, USA).
Dosages 1 μg/μl
Administration The solution was filtered and stereotactically injected into the right cerebral ventricle using the following coordinates: −0.8 mm anteroposterior, ±1.5 mm mediolateral, and −4.5 mm dorsoventral from the bregma.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 432.46
Formula C23H26F2N2O4
CAS Number 208255-80-5
Purity 100.00%
Solubility DMSO
Storage at -20°C
Customer Product Validations & Biological Datas
Source Oncol Lett (2017). Figure 6. DAPT (AbMole BioScience, Shanghai, China)
Method Co‑IP assay
Cell Lines SMMC‑7721 cells
Concentrations 1 μM
Incubation Time
Results The interaction between Jagged1 and Notch1 in SMMC‑7721 cells was also significantly reduced after adding DAPT compared with that of the normal serum group (P<0.01) (Fig. 6).
Rating
Source Oncol Lett (2017). Figure 5. DAPT (AbMole BioScience, Shanghai, China)
Method Western blot
Cell Lines SMMC‑7721 cells
Concentrations 1 μM
Incubation Time
Results The levels of Jagged1 and Notch1 were decreased after adding the Notch inhibitor, DAPT, indicating that DAPT successfully inhibited the Jagged1/Notch signaling pathway. In addition, the expression of VEGF protein was reduced after adding DAPT (Fig. 5).
Rating
Source Circ Res (2017). Figure 2. DATP (Abmole Bioscience)
Method Retina dissection and whole mount staining
Cell Lines mice
Concentrations 100 mg/kg
Incubation Time
Results DAPT treatment resulted in a large increase in vessel density and expansion of the vascular plexus in the postnatal retina of control mice (Fig. 2A, C, E, G). DAPT completely rescued the defect in SENP1-ecKO pups (Fig. 2B, D, F, H), which resulted in vascular length, vascular coverage, and tip sprouts growth comparable to the control group (Fig. 2I-K).
Rating
Source Sci adv (2015). Figure 5. The DAPT g-secretase inhibitor was obtained from AbMole BioScience.
Method Immunohistochemistry
Cell Lines
Concentrations 100 mg/kg, daily
Incubation Time
Results "The PlGF-modulated opposing vascular effects in relation to Dll4-Notch inhibition alter tumor growth by changing the microenvironment, tumor cell proliferation, and apoptosis."
Rating
Source Sci adv (2015). Figure 4. The DAPT g-secretase inhibitor was obtained from AbMole BioScience.
Method human tumor models, Immunohistochemistry
Cell Lines
Concentrations 100 mg/kg, daily
Incubation Time
Results PlGF mediates opposing vascular effects in nontreated and Dll4-Notch inhibitor–treated mouse tumors.
Rating
Source Sci adv (2015). Figure 3. The DAPT g-secretase inhibitor was obtained from AbMole BioScience.
Method Immunohistochemistry
Cell Lines Human JE-3, BeWo, MDA-MB-231 cells
Concentrations 100 mg/kg, daily
Incubation Time
Results "Both terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining and measurements of the activated or cleaved caspase 3 showed reductions of apoptotic cells in Dll4-Notch inhibitor–treated JE-3 and BeWo tumors. In contrast, treatment of PlGF-negative MDAMB-231 tumors with DAPT and Dll4 blockade showed completely opposite effects on cell proliferation and apoptosis, tipping the balance toward an apoptotic phenotype."
Rating
Source Sci adv (2015). Figure 1. The DAPT g-secretase inhibitor was obtained from AbMole BioScience.
Method Immunohistochemistry
Cell Lines Human JE-3, BeWo, MDA-MB-231 cells
Concentrations 100 mg/kg, daily
Incubation Time
Results "PlGF expression determines opposing effects of Dll4-Notch inhibition on human tumor growth and vascular remodeling."
Rating
Product Citations
References

A New Strategy for Discontinuation of Dual Antiplatelet Therapy: The RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation).
Kim BK et al. J Am Coll Cardiol. 2012 Sep 5. PMID: 22999717.

Stent thrombosis: insights on outcomes, predictors and impact of dual antiplatelet therapy interruption from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE trials.
Kedhi E et al. EuroIntervention. 2012 Sep 20;8(5):599-606. PMID: 22995087.

The γ-secretase inhibitor DAPT increases the levels of gangliosides at neuritic terminals of differentiating PC12 cells.
Oikawa et al. Neurosci Lett. 2012 Sep 6;525(1):49-53. PMID: 22867970.

Gamma-secretase inhibitor DAPT suppresses glioblastoma growth via uncoupling of tumor vessel density from vessel function.
Zou et al. Clin Exp Med. 2012 Jul 27. PMID: 22836313.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: DAPT, GSI-IX supplier, Gamma-secretase, inhibitors

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