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 7 Publications
4 Customer Reviews
Western blotting showing increased unconjugated SUMO1 levels in Notch1 ΔE cells treated with 10 uM DAPT for 3 days. Tubulin was used as a loading control.
Oncogene 2014 10.1038/onc.2014.319. DAPT (GSI-IX) purchased from Selleck.
R26PR;cre tumors express high levels of NICD and are sensitive to pharmacological inhibition of NOTCH1 signaling. (C) A cell line derived from R26PR;MMTV-cre tumor cells was cultured in the presence of a γ-secretase inhibitor, DAPT, or DMSO vehicle. Live cells were counted at 24, 48 and 72 hours of culture. (D) Western blot analysis of NICD following DAPT treatment.
Dis Model Mech 2013 6(6), 1494-506. DAPT (GSI-IX) purchased from Selleck.
Human corneal epithelial cells were subjected to a scratch assay and then treated with DAPT or DMSO (control) (A). The effect of DAPT concentration on scratch assay wound closure rate was measured (P < 0.001) (B). Western blot for Notch1IC confirmed that 10uM DAPT can effectively inhibit Notch activation (C). HCE-T cells pretreated with DAPT migrated 2.2 times faster than control in transwell migration assay (P < 0.0001) while Jagged1 treated cells migrated 20% slower but did not reach statistical significance (P =0.077) (D).
Invest Ophth Vis Sci 2012 53,12 . DAPT (GSI-IX) purchased from Selleck.
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2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.
|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||4% DMSO+corn oil||10mg/mL|
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT03008083||Not yet recruiting||Drug-Eluting Stents|Percutaneous Coronary Intervention||Shanghai MicroPort Medical (Group) Co., Ltd.||July 2017||Phase 4|
|NCT02605447||Recruiting||Coronary Artery Disease||Boston Scientific Corporation||January 2016||Phase 4|
|NCT02798913||Recruiting||Peripheral Artery Disease||Federico II University||January 2016||Phase 3|
|NCT02619760||Recruiting||Coronary Artery Disease||Kyoto University, Graduate School of Medicine||December 2015||Phase 4|
|NCT02601157||Recruiting||Stable Angina|Unstable Angina|Non-ST Segment Elevation Myocardial Infarction||Seoul National University Hospital|B. Braun Korea Co., Ltd.||December 2015||Phase 4|
|NCT02609698||Recruiting||Stable Angina, Unstable Angina, Silent Coronary Ischemia, Coronary Artery Disease||Ajou University School of Medicine|B. Braun Korea Co., Ltd.||August 2015||Phase 4|
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