Inhibitor of γ-secretase; causes a reduction in Aβ40 and Aβ42 levels in human primary neuronal cultures (IC50 values are 115 and 200 nM for total Aβ and Aβ42 respectively) and in brain extract, cerebrospinal fluid and plasma in vivo. Does not effect APPα and APPβ levels. Blocks Notch signaling in hybrid human-mouse fetal thymus organ culture (FTOC). Activity causes neural cells to commit to neuronal differentiation.

Dovey et al (2001) Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J.Neurochem. 76 173. 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 3498. El Mouedden et al (2006) Reduction in Abeta levels in Sprague Dawley rat after oral administration of the functional gamma-secretase inhibitor, DAPT: a novel non-transgenic model for Abeta production inhibitors. Curr.Pharmaceut.Des. 12 671.