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Stemgent Stemolecule DAPT

Code: 04-0041-base
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Stemolecule DAPT (also known as GSI-IX or LY-374973), a cell-permeable dipeptide, inhibits γ-secretase and indirectly inhibits Notch, a γ-secretase substrate1. Since the Notch pathway is involved in the development of both the nervous system and pancreas, DAPT may be useful in modulating Notch activity in embryonic stem cell differentiation studies2. DAPT has been shown to dose-dependently decrease amyloidβ levels via inhibition of γ-secretase in both plasma and cerebral spinal fluid3. Since amyloid β containing senile plaques are characteristic in Alzheimer's disease, DAPT may be useful in studies evaluating potential treatments for that disease.

Product Name

Stemolecule DAPT

Catalog Number

04-0041

Size

5 mg

Alternate Name(s)

GSI-IX
LY-374973
N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenylglycine-1,1-dimethylethyl ester

Chemical Formula

C23H26F2N2O4

Molecular Weight

432.46

CAS Number

208255-80-5

Purity

Greater than 99% by HPLC analysis

Formulation

White Powder

Solubility

For a 10 mM concentrated stock solution of DAPT, reconstitute the compound by adding 1.16 mL of DMSO to the entire contents of the vial. If precipitate is observed, warm the solution to 37 °C for 2 to 5 minutes. For cell culture, the media should be prewarmed prior to adding the reconstituted compound. Note: for most cells, the maximum tolerance to DMSO is less than 0.5%. This molecule is soluble in DMSO at 100 mM.

Storage and Stability

Store powder at 4 °C protected from light. Information about the stability of Stemolecules in solution is largely not available. As a general guideline, we recommend that stock solution be freshly made and stored in aliquots at −20 °C. The effect of storage of stock solutions should be verified for each application.

Quality Control

The purity of DAPT was determined by HPLC analysis. The accurate mass was determined by mass spectrometry. Cellular toxicity of DAPT was tested on mouse embryonic stem cells.

Specification Sheets

Safety Data Sheets

  1. Dovey, H. et al. Functional gamma-secretase inhibitors reduce β-amyloid peptide levels in brain. J Neurochem 76: 173-181 (2001).
  2. Crawford, T., and Roelink, H. The notch response inhibitor DAPT enhances neuronal differentiation in embryonic stem cell-derived embryoid bodies independently of sonic hedgehog signaling. Dev Dyn 236: 886-892 (2007).
  3. Lanz, T.A., Hosley, J.D., Adams, W.J., and Merchant, K.M. Studies of of Aβ pharmacodynamics in the brain, cererbrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the γ-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY-411575). J Pharmacol Exp Ther 309: 49-55 (2004).

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