Cas No.: | 208255-80-5 |
Chemical Name: | Dapt |
Synonyms: | DAPT;Glycine, N-[(3,5-difluorophenyl)acetyl]-L-alanyl-2-phenyl-,1,1-dimethylethyl ester, (2S)-;((S)-tert-butyl 2-((S)-2-(2-(3,5-difluorophenyl)acetamido)propanamido)-2-phenylacetate);(S)-tert-Butyl 2-((S)-2-(2-(3,5-difluorophenyl)acetamido)propanamido)-2-phenylacetate;DAPT DAPT;DAPT (GSI-IX);DAPT (GSI-IX, LY-374973);N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester(DAPT);N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester;tert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate;(3,5-Difluorophenylacetyl)-Ala-Phg-OtBu;(3,5-Difluorophenylacetyl)-L-alanyl-L-2-phenylglycine tert-Butyl Ester;GSI IX;GSI-IX;GSI-IX LY-374973 N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester;N-[N-(3,5-difluorophenylacetyl)-L-alanyl]-(S)-phenylglycine t-butyl ester;LY-374973;DAPT (enzyme inhibitor);(2S)-N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-2-phenylglycine tert-butyl ester;gamma-Secretase Inhibitor IX;InSolution™ gamma-Secretase Inhibitor IX;N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-Butyl Ester;GSIIX;PubChem22 |
SMILES: | FC1C([H])=C(C([H])=C(C=1[H])C([H])([H])C(N([H])[C@@]([H])(C([H])([H])[H])C(N([H])[C@]([H])(C(=O)OC(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1C([H])=C([H])C([H])=C([H])C=1[H])=O)=O)F |
Formula: | C23H26F2N2O4 |
M.Wt: | 432.4604 |
Sotrage: | 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO |
Description: | DAPT is a γ-secretase inhibitor with IC50s of 115 and 200 nM for total Aβ and Aβ42, respectively. |
In Vivo: | DAPT is administered to PDAPP mice (100 mg/kg s.c.) and the levels of DAPT and Aβ are examined in the brain cortex. Peak DAPT levels of 490 ng/g are achieved in the brain 3 h after treatment, and levels greater than 100 ng/g (~200 nM) are sustained throughout the first 18 h. These brain concentrations of DAPT are in excess of its IC50 for lowering Aβ in neuronal cultures (115 nM), and results in a robust and sustains pharmacodynamic effect[1]. DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and Nuclear factor kappa B in rats. Western blot analyses also show a significant decrease of Notch 1 and NF-κB expression in DAPT (0.03 mg/kg) group (P<0.05 vs. MCAO group)[3]. |
In Vitro: | DAPT inhibits Aβ production over 90%, effects only a modest reduction in APPβ in the culture media. Although APPβ is reduced by about 30% by DAPT treatment, this effect is not concentration-dependent and is reversed by the removal of DAPT[1]. CNE-2 cells are treated with increasing concentrations of DAPT (0, 25, 50 and 75 μM), and the γ-secretase-generated Notch 1 fragment Val1744-NICD is decreased after 48 h in a dose-dependent manner (P<0.01). The activation of γ-secretase is almost completely inhibited by DAPT at the concentration of 50 μM[2]. |