DAPT (GSI-IX),208255-80-5,IC-0199769

DAPT (GSI-IX) is an orally active γ-secretase inhibitor with IC50s of 115 nM and 200 nM for total amyloid-β (Aβ) and Aβ42 produced in human primary neuronal cultures, respectively.[1]
In vitro experiment it indicated that treatment with 10 μM DAPT significantly reduced the expression of Il6, Il12 and iNos at 6 and 12 h compared with vehicle at both low- and high-LPS stimulation.[2] In vitro, with 25, 50, and 100 μM DAPT in HepG2 cells significantly inhibited the proliferation and migration ability of HepG2 cells.[3] In vitro test shown it that treatment with 0, 25, 50 and 75 μM DAPT in CNE-2 cells, pre-treatment with DAPT enhanced the effect of cisplatin in a dose-dependent manner. However, the CNE-2 cells were treated with increasing concentrations of DAPT, and there was no obvious effect on cell survival.[5]
In vivo efficacy study it shown that treatment with 100 mg/kg DAPT subcutaneously in PDAPP mice, after 3 h the peak level of DAPT were 490 ng/g in the brain, and levels greater than 100 ng/g were sustained throughout the first 18 h.[1] DAPT (10, 30 and 100 mg/kg; p.o.) reduced the cortical total Aβ in a dose-dependent manner with a 50% reduction occuring at 100 mg/kg dosing.[1] In vivo test indicated it that DAPT was administered intragastrically once daily for 28 days in ICR mice that can effectively in ameliorating Cd-induced multi-organ damage and cognitive impairment in mice, because of DAPT restored abnormal performance in the Y-maze, forced swimming and Morris water maze (MWM) tests.[4]