YO-01027 is a dipeptidic gamma-secretase inhibitor with IC50 of 2.6 and 2.9 nM for the proteolysis of APPL and Notch, respectively. YO-01027 is used as an anti-Alzheimer agent. YO-01027 directly interact with the gamma-secretase complex. Unlike other gamma-secretase inhibitors,YO-01027 targets different functional domain of the complex. YO-01027 targets the N-terminal Presenilin fragment as well as another gamma-secretase inhibitor Compound E (Cpn E), whereas DFK167 and DAPT, another two gamma-secretase inhibitors, bind to the catalytic site of the Presenilin aspartyl protease subunit and the C-terminal Presenilin fragment, respectively. In a study, YO-01027 and CpnE indicated no apparent discrimination in blocking APPL and Notch cleavages, displaying statistically equivalent IC50 values for both substrates.[1] |
