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γ-Secretase Inhibitor XI is a cell-permeable, active site directed, irreversible serine protease inhibitor that belongs to the class of isocoumarin analogs. The compound acts as a potent and selective inhibitor of γ-secretase and blocks the production of both amyloid-β40 and Aβ42 in HEK293 cells expressing wild-type and Swedish-mutant β-amyloid precursor protein (APP).
1. Harper, J W., et al., 1985. Reaction of serine proteases with substituted 3-alkoxy-4-chloroisocoumarins and 3-alkoxy-7-amino-4-chloroisocoumarins: new reactive mechanism-based inhibitors. Biochemistry. 24(25): 7200-13. PMID: 3910097
2. Kerrigan, J E., et al., 1995. Mechanism-based isocoumarin inhibitors for human leukocyte elastase. Effect of the 7-amino substituent and 3-alkoxy group in 3-alkoxy-7-amino-4-chloroisocoumarins on inhibitory potency. Journal of medicinal chemistry. 38(3): 544-52. PMID: 7853347
3. Petit, A., et al., 2001. New protease inhibitors prevent gamma-secretase-mediated production of Abeta40/42 without affecting Notch cleavage. Nature cell biology. 3(5): 507-11. PMID: 11331880
4. Esler, William P., et al., 2002. Amyloid-lowering isocoumarins are not direct inhibitors of gamma-secretase. Nature cell biology. 4(5): E110-1; author reply E111-2. PMID: 11988746
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