Catalog No.S2215 Synonyms: LY-374973
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.
Cited by 51 Publications
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Choose Selective Gamma-secretase Inhibitors
|Description||DAPT (GSI-IX) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells.|
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.  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. 
|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.  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. |
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.
|In vitro||DMSO||86 mg/mL (198.86 mM)|
|Ethanol||50 mg/mL (115.61 mM)|
|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.
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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||--|
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.
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Frequently Asked Questions
Could you please help test the formulation of S2215 for in vivo studies?
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.
I would like to ask if you would recommend this product used in endothelial cells (e.g. both murine and human endothelial cells).
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/