Biological Activity
Aloxistatin (E64d) is a cell-permeable and irreversible broad-spectrum cysteine protease inhibitor.
In Vitro
Inhibition of protease-resistant prion protein (PrP-res) accumulation in ScNB cells by cysteine protease inhibitor Aloxistatin (E64d) with IC50 of 0.5±0.11 μM. For the cell surface PrP-sen detection, PrP-sen is immunoprecipitated from media treated with phosphatidylinositol-specific phospholipase C (PIPLC) to release pulse-35S-labeled PrP-sen from the cell surface. Aloxistatin is maintained at 15 μM, respectively, in the labeling media of all but the control cells [1]. Aloxistatin (E64d) (which specifically blocks cysteine proteases, but not serine proteases such as granzymes) is able to completely block turnover of the CatL substrate Z-Phe-Arg-aminomethylcoumarin, when pre-incubated with NK-92 or YT 5 cells[2]. Aloxistatin (E64d) is a broad-spectrum cell-permeable inhibitor of cysteine proteases[3].
In Vivo
Oral administration of Aloxistatin (E64d) to guinea pigs results in a dose-dependent reduction in brain, CSF and plasma Aβ(40) and Aβ(42). Aloxistatin also causes a biphasic dose-dependent reduction in brain CTFβ. Aloxistatin causes a dose-dependent increase in brain sAβPPα. The mean sAβPPα levels are significantly higher than the no dose group for Aloxistatin doses of 5 mg/kg/day or greater with the highest Aloxistatin dose resulting in the maximum increase in sAβPPα of about 54% more than the control group. Similar to the Aβ effect, oral Aloxistatin administration produces a biphasic dose-dependent reduction in brain cathepsin B activity. The minimum effective dose is about 1 mg/kg/day with the highest Aloxistatin dose causing the maximum reduction in brain cathepsin B activity of about 91% lower than that of the control group. Thus, Aloxistatin reduces guinea pig brain cathepsin B activity in a manner which is consistent with the compound inhibiting cathepsin B β-secretase activity[4]. Aloxistatin (E64d) inhibits the increases in the expression of AT1AR and ACE genes in rats. Administration of Olmesartan or Aloxistatin reduces the increase in the superoxide production of the intramyocardial coronary arteries in HF rats[5].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.