DAPT | gamma-secretase inhibitor

DAPT (208255-80-5) is an inhibitor of γ-secretase (IC₅₀ in human primary neurons = 115 nM for total Aβ or 200 nM for Aβ42 specifically).¹ Oral administration of DAPT has been shown to reduce levels of Aβ in brain extract, cerebrospinal fluid and plasma from mice and rats.^2,3 DAPT blocks Notch signaling which promotes neuronal differentiation of precursor cells.⁴ Enhances iPS cells without oncogenes KLF4 and CMYC⁵. Cell permeable.

References/Citations:

1) Dovey et al. (2001), Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain; J. Neurochem., 76 173
2) Portelius et al. (2009), Effects of γ-secretase inhibition on the amyloid β isoform pattern in a mouse model of Alzheimer’s disease; Cell Signal., 5 615
3) El Moueddon et al. (2006), 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. Pharma. Des., 12 1671
4) De Smedt et al. (2005), Different thresholds of notch signaling bias human precursor cells towards B-, NK-, monocytic/dendritic, or T-cell lineage in thymus microenvironment; Blood, 106 2236
5) Ichida et al. (2014), Notch inhibition allows oncogene-independent generation of iPS cells; Nature Chem. Biol., 10 632