DAPT is a functional γ-secretase inhibitor and significantly reduces the production of total Aβ and Aβ42 in human primary neuronal cultures (IC₅₀= 115 nM for total Aβ, IC₅₀= 200 nM for Aβ42) ^[1], as well as in brain extract, CSF, and the plasma in vivo dose- and time-dependently ^[2]. DAPT efficiently blocks Notch signaling in hybrid human-mouse fetal thymus organ culture (FTOC) ^[3]. DAPT decreases lymphoproliferation in CBA-lpr mice and autoimmunity in MRL-lpr mice. By using a novel intermittent low-dose schedule, DAPT is well tolerated for months and the reported side effects of γ-secretase inhibitor are avoided ^[4]. DAPT-mediated suppression of Notch response enhances neuronal differentiation in ESCs-derived embryoid bodies (EBs) independently of SHH signaling ^[5].

Chemical Properties