title: γ-Secretase modulators: current status and future directions.
abstract: This chapter reviews the current status of γ-secretase modulators, highlighting key compounds by each company involved in the area. The review focuses on the three main chemotypes: acids, imidazoles and related derivatives and natural products. A section on chemical biology and ligand-binding site elucidation studies is also included. The primary source of information is drawn from peer reviewed literature as this permits analysis of PK-PD relationships and subsequent comment. Discussion of the patent literature is included for completeness. From this analysis, the key issues and challenges in the area are highlighted. The review concludes with a summary of the clinical development status and comment on future prospects of the field.
authors.affiliation: Department of Chemistry, Discovery Research, Neuroscience and General Medicine Product Creation Unit, Eisai Ltd., EMEA Knowledge Centre, Mosquito Way, Hatfield, United Kingdom.
authors.forename: Adrian
authors.initials: A
authors.lastname: Hall
authors.affiliation: Department of BioPharmacology, Discovery Research, Neuroscience and General Medicine Product Creation Unit, Eisai Ltd., EMEA Knowledge Centre, Mosquito Way, Hatfield, United Kingdom.
authors.forename: Toshal R
authors.initials: TR
authors.lastname: Patel
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use
chemical_list: D007093:Imidazoles; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; γ-Secretase; γ-Secretase inhibitors; γ-Secretase modulators