Stemolecule™ DAPT

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.

Stemgent and the Stemolecule brand name are trademarks of REPROCELL Inc., Japan.

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:

• 04-0041 Specifications Sheet

Safety Data Sheets:

• 04-0041 Safety Data Sheet

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 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).

Additional Publications

• Fernandes HJR; Patikas M; Foskolou S; Field SF; Park J-E; Myrne ML; Bassett AR; Metzakopian E. Single-Cell Transcriptomics of Parkinson’s Disease Human In Vitro Models Reveals Dopamine Neuron-Specific Stress Responses. Cell Reports 33:108263 (2020).
• Durens M; Nestor J; Herold K Niescier RF; Lunden FW; Phillips AW; Lin Y-C; Nestor MW. High-content interrogation of human induced pluripotent stem cell-derived cortical organoid platforms. bioRxiv http://dx.doi.org/10.1101/697623. : (2019).
• Wang L; De Solis AJ; Goffer Y; Birkenback KE; Engle SE; Tanis R; Levenson JM; Lu X; Rausch R: Purohit M; Lee J-Y; Tan J; De Rosa MC; DOege CA; Aaron HL; Martins G; Brüning JC; Egli D; Costa R; Berbari N; Leibel RL; Stratigopoulos G. Ciliary gene RPGRIP1L is required for hypothalamic arcuate neuron development. JCI Insight 4:e123337 (2019).
• Sluch VM; Chamling X; Liu MM; Berlinicke CA; Cheng J; Mitchell KL; Welsbie DS; Zack DJ. Enhanced Stem Cell Differentiation and Immunopurification of Genome Engineered Human Retinal Ganglion Cells. Stem Cells Translat Med 6:1972 (2017).
• Portelius, E., Zhang, B., Gustavsson, M.K., Brinkmalm, G., Westman-Brinkmalm, A., Zetterberg, H., Lee, V.M., Trojanowski, J.Q., and Blennow, K. Effects of gamma-secretase inhibition on the amyloid β isoform pattern in a mouse model of Alzheimer's disease. Neurodegener Dis 6: 258-262 (2009).
• El Mouedden, M., Vandermeeren, M., Meert, T., and Mercken, M. Reduction of Aβ levels in the Sprague Dawley rat after oral administration of the functional γ-secretase inhibitor, DAPT: a novel non-transgenic model for Aβ production inhibitors. Curr Pharm Des 12: 671-676 (2006).
• De Smedt, M., Hoebeke, I., Reynvoet, K., Leclercq, G., and Plum, J. Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment. Blood 106: 3498-3506 (2005).