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Passive immunotherapy with a novel antibody against 3pE-modified Abeta demonstrates potential for enhanced efficacy and favorable safety in combination with BACE inhibitor treatment in plaque-depositing mice.
Janssens J, Hermans B, Vandermeeren M, Barale-Thomas E, Borgers M, Willems R, Meulders G, Wintmolders C, Van den Bulck D, Bottelbergs A, Ver Donck L, Larsen P, Moechars D, Edwards W, Mercken M, Van Broeck B. Janssens J, et al. Neurobiol Dis. 2021 Jul;154:105365. doi: 10.1016/j.nbd.2021.105365. Epub 2021 Apr 10. Neurobiol Dis. 2021. PMID: 33848635 Free article.
Heparin derivatives as inhibitors of BACE-1, the Alzheimer's beta-secretase, with reduced activity against factor Xa and other proteases.
Patey SJ, Edwards EA, Yates EA, Turnbull JE. Patey SJ, et al. J Med Chem. 2006 Oct 5;49(20):6129-32. doi: 10.1021/jm051221o. J Med Chem. 2006. PMID: 17004727
Heparan sulfate (HS) regulates processing of the amyloid precursor protein by the Alzheimer's beta-secretase (BACE-1). An HS analogue, porcine intestinal mucosal heparin, was systematically modified at the principal positions of O-sulfation and N-sulfation/acetylation and …
Heparan sulfate (HS) regulates processing of the amyloid precursor protein by the Alzheimer's beta-secretase (BACE-1). An HS analogue …
Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease.
Goetzl EJ, Mustapic M, Kapogiannis D, Eitan E, Lobach IV, Goetzl L, Schwartz JB, Miller BL. Goetzl EJ, et al. FASEB J. 2016 Nov;30(11):3853-3859. doi: 10.1096/fj.201600756R. Epub 2016 Aug 10. FASEB J. 2016. PMID: 27511944 Free PMC article.
BACE-1 levels also were a mean of 7-fold higher in ADEs than in NDEs from cultured rat type-specific neural cells. ...ADE cargo proteins may be useful for studies of mechanisms of cellular interactions and effects of BACE-1 inhibitors in AD.-Goetzl, E. J., Mustapic, …
BACE-1 levels also were a mean of 7-fold higher in ADEs than in NDEs from cultured rat type-specific neural cells. ...ADE cargo prote …
Discovery of a novel warhead against beta-secretase through fragment-based lead generation.
Geschwindner S, Olsson LL, Albert JS, Deinum J, Edwards PD, de Beer T, Folmer RH. Geschwindner S, et al. J Med Chem. 2007 Nov 29;50(24):5903-11. doi: 10.1021/jm070825k. Epub 2007 Nov 7. J Med Chem. 2007. PMID: 17985861
Problems arising due to our inability to grow BACE-1 crystals at the biologically relevant pH at which the screen was run were overcome by using endothiapepsin as a surrogate aspartyl protease. Among others, we identified 6-substituted isocytosines as a novel warhead again …
Problems arising due to our inability to grow BACE-1 crystals at the biologically relevant pH at which the screen was run were overco …
Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase.
Congreve M, Aharony D, Albert J, Callaghan O, Campbell J, Carr RA, Chessari G, Cowan S, Edwards PD, Frederickson M, McMenamin R, Murray CW, Patel S, Wallis N. Congreve M, et al. J Med Chem. 2007 Mar 22;50(6):1124-32. doi: 10.1021/jm061197u. Epub 2007 Feb 22. J Med Chem. 2007. PMID: 17315857
Fragment-based lead discovery has been successfully applied to the aspartyl protease enzyme beta-secretase (BACE-1). Fragment hits that contained an aminopyridine motif binding to the two catalytic aspartic acid residues in the active site of the enzyme were the chemical s …
Fragment-based lead discovery has been successfully applied to the aspartyl protease enzyme beta-secretase (BACE-1). Fragment hits th …
Application of fragment-based lead generation to the discovery of novel, cyclic amidine beta-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency.
Edwards PD, Albert JS, Sylvester M, Aharony D, Andisik D, Callaghan O, Campbell JB, Carr RA, Chessari G, Congreve M, Frederickson M, Folmer RH, Geschwindner S, Koether G, Kolmodin K, Krumrine J, Mauger RC, Murray CW, Olsson LL, Patel S, Spear N, Tian G. Edwards PD, et al. J Med Chem. 2007 Nov 29;50(24):5912-25. doi: 10.1021/jm070829p. Epub 2007 Nov 7. J Med Chem. 2007. PMID: 17985862
Fragment-based lead generation has led to the discovery of a novel series of cyclic amidine-based inhibitors of beta-secretase (BACE-1). Initial fragment hits with an isocytosine core having millimolar potency were identified via NMR affinity screening. ...Similarity searc …
Fragment-based lead generation has led to the discovery of a novel series of cyclic amidine-based inhibitors of beta-secretase (BACE- …