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.
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