DAPT

DAPT is a γ-secretase inhibitor (with IC50s of 115 and 200 nM for total Aβ and Aβ42, respectively) that can reduce Aβ40 and Aβ42 levels in human primary neuronal cells and brain extracts, DAPT also inhibits γ-secretase complex and indirectly inhibits Notch, a γ-secretase substrate (Dovey, et al). Its activity causes neural cells to commit to neuronal differentiation (Crawford et al) and has been shown to reduce colony-forming efficiency in mouse neural stem cells (Androutsellis-Theotokis et al). DAPT has also been shown to promote differentiation of pancreatic cells from human pluripotent stem cells (D’Amour et al).

Alternative names: GSI-IX; GSI IX, γ-Secretase Inhibitor IX, LY-374973
Applications: induction of neurons from hiPSCs, generation of midbrain dopaminergic neurons from hPSCs
Cell types: Neurons, iPSCs, hepatocytes, retinal organoids

Keywords: DAPT, γ-secretase, gamma-secretase, inhibitors, proteases, β-Amyloid, beta-Amyloid, b-amyloid, Precursor, peptides, organoids, notch, gamma-secretase, beta cell, neural cell, retinal stem cells

Documents

• Technical Data Sheet
• Brochure: Small Molecules for Stem Cell Research
• FAQs: General Guide for Small Molecules

References and Publications

• Feng, J., (2019) DAPT, a γ-Secretase Inhibitor, Suppresses Tumorigenesis, and Progression of Growth Hormone-Producing Adenomas by Targeting Notch Signaling. Front. Oncol.
• Crawford, T.Q., et al. (2007) 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.
• D’Amour, K.A., et al. (2006) Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 24: 1392-1401.
• Androutsellis-Theotokis, A., et al. (2006) Notch signaling regulates stem cell numbers in vitro and in vivo. Nature 442: 823-826.
• Dovey, H.F., et al. (2001) Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem 76: 173-181.