DAPT (GSI-IX)

Catalog No.S2215 Synonyms: LY-374973

DAPT (GSI-IX) Chemical Structure

Molecular Weight(MW): 432.46

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

Size Price Stock Quantity  
In DMSO USD 112 In stock
USD 70 In stock
USD 120 In stock
USD 210 In stock
USD 370 In stock
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Cited by 51 Publications

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Biological Activity

Description DAPT (GSI-IX) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells.
Targets
γ secretase(Aβ) [1]
(HEK 293 cells)
20 nM
In vitro

In human primary neuronal cultures, DAPT also shows inhibitory effects on Aβ production with IC50 of 115 nM and 200 nM respectively for Aβ total and Aβ42, which is 5-10-fold lower than is observed in HEK 293 cells. [1] A recent study shows that DAPT inhibits the proliferation of SK-MES-1 cells in a concentration-dependent manner with IC50 of 11.3 μM. In addition, DAPT also induces caspase-dependent and caspase-independent apoptosis in lung squamous cell carcinoma cells by inhibiting Notch receptor signaling pathway. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A549 CD133− MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWLFU4RjOiEQvF2= M3:z[FQ5KGh? NWfMc4I6\W6qYX7j[ZMh[2WubDDndo94fGhiaX7obYJqfGmxbjDpcoR2[2WmIHL5JGNFTFB? NXj4PJQ5OjR3MEK5OFk>
A549 CD133+ NHnvVWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1PCcFIh|ryP MonhOFghcA>? Mnzq[Y5p[W6lZYOgZ4VtdCCpcn;3eIghcW6qaXLpeIlwdiCrbnT1Z4VlKGK7IFPESHA> Ml\vNlQ2ODJ7NEm=
HT29  MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn:xNE42NTd3IN88US=> MWSxNk8zPC92ODDo MXjEUXNQ M4HXVolvcGmkaYTzJJRp\SClZXzsJIdzd3e2aDDpckBiKGOxbnPlcpRz[XSrb36gcYFvdmW{ MmfTNlUzPTd7NEW=
SHG-44 NYnGS5ZJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mlm3NE42NTFyIN88US=> NF3DPJQyNTViZB?= MYDpcohq[mm2czD0bIUh[2WubDD2bYFjcWyrdImgZZQhfGinIH;weIlu[WxiY3;uZ4VvfHKjdHnvckBw\iBzIN88US=> M3vne|I2ODZ|Mki1
MG63 MV3GeY5kfGmxbjDBd5NigQ>? NHPCT24yODBizszN NHTEN|MzPCCq MUXEUXNQ MVnk[ZNmdnOrdHn6[ZMhfGinIHPlcIwhdGmwZTD0c{BkcXOybHH0bY4hfHKnYYTt[Y51 MlvPNlQ5QTR{OUe=
Saos-2 Mle2SpVv[3Srb36gRZN{[Xl? NV3jdJZ1OTByIN88US=> MlrsNlQhcA>? NVK5UYRMTE2VTx?= MV\k[ZNmdnOrdHn6[ZMhfGinIHPlcIwhdGmwZTD0c{BkcXOybHH0bY4hfHKnYYTt[Y51 M{DGeVI1QDl2Mkm3
U251 MkPzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYiyJO69VQ>? MWW0PEBp MlO2SG1UVw>? M1LKPZN1emWwZ4To[Y5{yqC2LVHVR2IucW6mdXPl[EBk\WyuIHfyc5d1cCC|dYDwdoV{e2mxbh?= M1OwWFI1Pzl|M{Gz
U87  M1rQZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXXz[lJGOiEQvF2= NYTWXoN4PDhiaB?= NXT5Nmx5TE2VTx?= M1PMcJN1emWwZ4To[Y5{yqC2LVHVR2IucW6mdXPl[EBk\WyuIHfyc5d1cCC|dYDwdoV{e2mxbh?= M4j5XVI1Pzl|M{Gz
U251 M3H5W2Z2dmO2aX;uJGF{e2G7 MVOyJO69VQ>? NFu4OnQ1QCCq M4nWNGROW09? NEXLOFVjdG:la4RCpJQuSVWFQj3pcoR2[2WmIHHjeIl3[XSrb36gc4YhfGinIICzPEBOSVCNL13BVGtCWEt{L1jzdFI4KHCjdHj3ZZkh[W6mIHnubIljcXS|IHX4dJJme3Orb36gc4YhVkmFREG= NY\iN4hvOjR5OUOzNVM>
U87  M1\lZmZ2dmO2aX;uJGF{e2G7 Ml7DNkDPxE1? M4DkV|Q5KGh? NHO5TIpFVVOR NUXncpBP[myxY3vzxsB1NUGXQ1KtbY5lfWOnZDDhZ5RqfmG2aX;uJI9nKHSqZTDwN|ghVUGSSz;NRXBMSVCNMj;Id5AzPyCyYYToe4F6KGGwZDDpcohq[mm2czDlfJBz\XO|aX;uJI9nKE6LQ1Sx M3LJ[|I1Pzl|M{Gz
A549  NIn5[JdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmCyNVAh|ryP NV\xeGRKOjSq M2npXYRm[3KnYYPld{B1cGViY3XscEB3cWGkaXzpeJkh[2:vYnnu[YQhf2m2aDDQWGU> MVWyN|Y4OTZzOR?=
GC-B  MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYHWT2Z[Pi5{NT2xNFAh|ryP MoL0NlQhcA>? NWPUVYdmTE2VTx?= MYHpcohq[mm2czD0bIUh[2WubDDndo94fGhiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ? NFrFVWEyQTV2MkS0Oi=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
Snail / N-cadherin / Vimentin / E-cadherin; 

PubMed: 24932308     


EMT markers were analyzed in AGS and MKN45 cells by immunoblotting following treatment with DAPT or the DMSO control.

Bax / caspase-3 / Bcl-2; 

PubMed: 29487808     


Western blot analysis of Bax, caspase-3, and Bcl-2 protein expression.

NICD / Pax7 / Pax3 / MyoD / Myogenin / p21; 

PubMed: 18957511     


(A) Primary myoblasts, incubated in GM until 90–100% confluency, were transferred to DM and were incubated for 1 day in the presence of DMSO or 5 μM GM6001, a metalloproteinase inhibitor (left), or in the presence of DMSO or 1 μM DAPT, a γ-secretase inhibitor (right). The levels of NICD, Pax7, Pax3, MyoD, myogenin, and p21 were determined by Western blotting, tubulin is a gel-loading control. A representative experiment out of three is shown.

24932308 29487808 18957511
Growth inhibition assay
Cell viability; 

PubMed: 27118928     


Cell viability of CPH036 or CPH047 cells following 7 days of treatment with iressa, DAPT or a combination in the indicated doses (mean ± SEM, n = 5). *p < 0.05, **p < 0.01, ***p < 0.001.

27118928
Immunofluorescence
CDK5; 

PubMed: 18662245     


Fixed E18 rat embryonic cortical neurons cells were immunostained for cdk5 (a, e) and p35 (b, f). Nuclei are stained with DAPI (c, g). Immunostaining for cdk5, p35 and DAPI are merged (d, h).

18662245
In vivo DAPT administration (100mg/kg) leads to a robust and sustained pharmacodynamic effect in PDAPP mice that DAPT levels in the brain exceeds 100 ng/g within 1 hour and persists up to 18 hours after administration, with peak levels of 490 ng/g observed after 3 hour. And during the period, DAPT (100 mg/kg) also reduces the cortical total Aβ and Aβ42 in a dose-dependent manner with a 50% reduction. [1] In rat cerebral cortexes, DAPT (40 mg/kg) suppresses the LPS-induced activity of γ-secretase and increases the cell apoptosis with the prolonged neuroinflammation. [3]

Protocol

Kinase Assay:[1]
+ Expand

In vitro Aβ reduction assays :

Human embryonic kidney cells (American Type Culture Collection CRL-1573), 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. DAPT are diluted from stock solutions in dimethylsulfoxide (DMSO) to yield a final concentration equal to 0.1% DMSO in media. Cells are pre-treated for 2 hours at 37 °C with DAPT, media are aspirated off and fresh compound solutions applied. After an additional 2-hour treatment period, conditioned media is 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. Human and PDAPP mouse neuronal cultures are grown in serum-free media to enhance their neuronal characteristics, and appeared to be greater than 90% neurons after maturation prior to use. Conditioned media to establish baseline Aβ values are collected by adding fresh media to each well and incubated for 24 hours at 37 °C in the absence of DAPT. Cultures are then treated with fresh media containing DAPT at the desired range of concentrations for an additional 24 hours at 37 °C, and conditioned media collected. For the measurement of total Aβ, samples are analyzed with the same ELISA (266–3D6) as used for the HEK 293 cell assays. Analyses of samples for Aβ42 production are performed by a separate ELISA (21F12–3D6) that utilizes a capture antibody specific for the Aβ42 C-terminus. Inhibition of production for both total Aβ and Aβ42 are determined by the difference between the values for the compound treatment and baseline periods. After plotting percentage inhibition versus DAPT concentration, data are analyzed with XLfit software, as above, to determine potency.
Cell Research:[2]
+ Expand
  • Cell lines: SK-MES-1
  • Concentrations: 2.5 μM to 160 μM
  • Incubation Time: 72 hours
  • 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. α-MEM supplemented with the same amount of MTT solution and solvent is used as blank solution. The IC50 value is calculated using PROBIT program in SPSS.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Heterozygous PDAPP transgenic mice overexpressing the APPV717F mutant form of the amyloid precursor protein.
  • Formulation: DAPT is dissolved in corn oil, 5% (v/v) ethanol.
  • Dosages: ≤100 mg/kg
  • Administration: Administered via p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 86 mg/mL (198.86 mM)
Ethanol 50 mg/mL (115.61 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
4% DMSO+corn oil
For best results, use promptly after mixing.
10mg/mL

* 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 432.46
Formula

C23H26F2N2O4

CAS No. 208255-80-5
Storage powder
in solvent
Synonyms LY-374973

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03567733 Active not recruiting Device: XIENCE Sierra Ischemic Heart Disease|Coronary Artery Disease Fundación EPIC June 18 2018 --
NCT03190005 Unknown status Drug: clopidogrel|Drug: Placebos Stable Angina Taipei City Hospital January 1 2017 Not Applicable
NCT02548650 Completed Drug: Vorapaxar|Drug: Clopidogrel|Drug: Aspirin Myocardial Infarction|Diabetes Mellitus|Peripheral Arterial Disease University of Florida|Merck Sharp & Dohme Corp. March 25 2016 Phase 4
NCT03362463 Active not recruiting Other: Non-Interventional Study Acute Coronary Syndrom AstraZeneca December 28 2015 --
NCT03103620 Completed Device: COBRA PzF Coronary Stent System Stable Angina|Unstable Angina|ACS - Acute Coronary Syndrome|STEMI|NSTEMI - Non-ST Segment Elevation MI|Myocardial Infarction CeloNova BioSciences Inc.|AlpinARC September 10 2015 --
NCT03011879 Unknown status Other: clinical pathway ST-Elevation Myocardial Infarction Peking University First Hospital|Chinese Medical Doctor Association July 2015 --

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Frequently Asked Questions

  • Question 1:

    Could you please help test the formulation of S2215 for in vivo studies?

  • Answer:

    S2215 DAPT in 30% PEG400+0.5% Tween80+5% Propylene glycol at 10 mg/ml is a suspension. We tried to add some EtOH, and it dissolved clearly in organice solvents, but when water added, the precipitation went out immediately. Then we tried other vehicles, and found S2215 can be dissolved in 4% DMSO+corn oil at 10 mg/ml clearly.

  • Question 2:

    I would like to ask if you would recommend this product used in endothelial cells (e.g. both murine and human endothelial cells).

  • Answer:

    I think DAPT can be used in endothelial cells from both human and mouse, please see the following reference: http://www.ncbi.nlm.nih.gov/pubmed/19481797; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615564/

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID