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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8 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.

    A panel of GICs was treated with the indicated doses of DAPT for 48 hours. γSecretase inhibitors inhibited expression of NICD, Hes1, Hes3, and Hes5 in a dose-dependent manner.

    Stem Cells 2014 32(1), 301-12. DAPT (GSI-IX) purchased from Selleck.

  • Upper; Effect of DAPT, a Notch inhibitor on Notch4-ICD expression in TAMR-MCF-7 cells. Lower; Effect of DAPT on cell proliferation of TAMR-MCF-7 cells. Cells were exposed to DAPT (0.3-10 μM) and cell proliferation was measured at different time points by MTT assay. Data represent mean ± SD with 6 different samples.

    cancer lett, 2017, 390:115-125. DAPT (GSI-IX) purchased from Selleck.

    Representative E-cadherin staining in MCF-7 and TAMR-MCF-7 cells.

    cancer lett, 2017, 390:115-125. DAPT (GSI-IX) purchased from Selleck.

  • (E) Western blotting analysis shows DAPT decrease HES1, ALDH1, BMI1 and SOX2 expression in HNSCC CAL27 cell line.

    Sci Rep, 2016, 6:24704. 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.

  • Effects of endosulfan on cytoskeleton and mitosis in HUVECs. Images 7–12 are the 4 × magnified versions of 1–6, respectively. Microfilament (A), microtubule (B), and cell nucleus (C) were incubated with Actin-Tracker Green, Tubulin-Tracker Red, and Hoechst 33258 solution, respectively.

    Environ Pollut, 2017, 221:26-36. 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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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− M1rDUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUTNOG5pOiEQvF2= NYL6Omg3PDhiaB?= MYPlcohidmOnczDj[YxtKGe{b4f0bEBqdmirYnn0bY9vKGmwZIXj[YQh[nliQ1TEVC=> NXfvV251OjR3MEK5OFk>
A549 CD133+ M{W1OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4LpOFIh|ryP MYO0PEBp MlvY[Y5p[W6lZYOgZ4VtdCCpcn;3eIghcW6qaXLpeIlwdiCrbnT1Z4VlKGK7IFPESHA> M4GzNVI1PTB{OUS5
HT29  NWLWdI4zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1\3WlAvPS15NTFOwG0> M1nGTFEzNzJ2L{S4JIg> NUDYcXRjTE2VTx?= Mn;ZbY5pcWKrdIOgeIhmKGOnbHyg[5Jwf3SqIHnuJIEh[2:wY3XueJJifGmxbjDtZY5v\XJ? MYeyOVI2Pzl2NR?=
SHG-44 MmjRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{flfVAvPS1zMDFOwG0> NWTPVXcxOS13IHS= M1:4RYlvcGmkaYTzJJRp\SClZXzsJJZq[WKrbHn0fUBifCC2aHWgc5B1cW2jbDDjc45k\W62cnH0bY9vKG:oIEGg{txO MVqyOVA3OzJ6NR?=
MG63 MULGeY5kfGmxbjDBd5NigQ>? MWCxNFAh|ryP MmDwNlQhcA>? MUDEUXNQ NHXTOmRl\XOnboPpeIl7\XNidHjlJINmdGxibHnu[UB1dyClaYPwcIF1cW5idILlZZRu\W62 MX2yOFg6PDJ7Nx?=
Saos-2 NY\4SppMTnWwY4Tpc44hSXO|YYm= NUDsO5U2OTByIN88US=> MmqwNlQhcA>? M1noRmROW09? MVTk[ZNmdnOrdHn6[ZMhfGinIHPlcIwhdGmwZTD0c{BkcXOybHH0bY4hfHKnYYTt[Y51 NHizOmgzPDh7NEK5Oy=>
U251 NGfmXo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDjNkDPxE1? MYO0PEBp MVTEUXNQ NXOydXJwe3S{ZX7neIhmdnQEoIStRXVESi2rbnT1Z4VlKGOnbHyg[5Jwf3SqIIP1dJBz\XO|aX;u MXqyOFc6OzNzMx?=
U87  MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkHkNkDPxE1? M1\uflQ5KGh? M{LaOmROW09? M3:xSpN1emWwZ4To[Y5{yqC2LVHVR2IucW6mdXPl[EBk\WyuIHfyc5d1cCC|dYDwdoV{e2mxbh?= NGPBSGEzPDd7M{OxNy=>
U251 MX\GeY5kfGmxbjDBd5NigQ>? M3TnOlIh|ryP NFz4[2U1QCCq M1rGeWROW09? MnLhZoxw[2u|wrD0MWFWS0JvaX7keYNm\CCjY4TpeoF1cW:wIH;mJJRp\SCyM{igUWFRUy:PQWDLRXBMOi:Kc4CyO{Bx[XSqd3H5JIFv\CCrbnjpZol1eyCneIDy[ZN{cW:wIH;mJG5KS0Rz MUOyOFc6OzNzMx?=
U87  MnTqSpVv[3Srb36gRZN{[Xl? MnnWNkDPxE1? NH3FV3c1QCCq NEDDOYtFVVOR NXrnUpRI[myxY3vzxsB1NUGXQ1KtbY5lfWOnZDDhZ5RqfmG2aX;uJI9nKHSqZTDwN|ghVUGSSz;NRXBMSVCNMj;Id5AzPyCyYYToe4F6KGGwZDDpcohq[mm2czDlfJBz\XO|aX;uJI9nKE6LQ1Sx MXGyOFc6OzNzMx?=
A549  MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3LcnUyOCEQvF2= MlXWNlRp NX\ZVmlo\GWlcnXhd4V{KHSqZTDj[YxtKH[rYXLpcIl1gSClb33ibY5m\CC5aYToJHBVTQ>? NIPJVWkzOzZ5MU[xPS=>
GC-B  M1r3SGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XlT|YvOjVvMUCwJO69VQ>? NIK1VXozPCCq MXTEUXNQ NI\K[XhqdmirYnn0d{B1cGViY3XscEBoem:5dHigbY4h[SCmb4PlMYRmeGWwZHXueEBu[W6wZYK= M3HqOFE6PTR{NES2

... Click to View More Cell Line Experimental Data

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 individually and in order:
4% DMSO+corn oil
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
Synonyms LY-374973

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Tech Support

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

  • 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