title: Progress and developments in tau aggregation inhibitors for Alzheimer disease.
abstract: Pharmacological approaches directed toward Alzheimer disease are diversifying in parallel with a growing number of promising targets. Investigations on the microtubule-associated protein tau yielded innovative targets backed by recent findings about the central role of tau in numerous neurodegenerative diseases. In this review, we summarize the recent evolution in the development of nonpeptidic small molecules tau aggregation inhibitors (TAGIs) and their advancement toward clinical trials. The compounds are classified according to their chemical structures, providing correlative insights into their pharmacology. Overall, shared structure-activity traits are emerging, as well as specific binding modes related to their ability to engage in hydrogen bonding. Medicinal chemistry efforts on TAGIs together with encouraging in vivo data argue for successful translation to the clinic.
authors.affiliation: Laboratory of Organic Synthesis of Functional Systems, Humboldt-Universität zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin, Germany. bruno.bulic@huberlin.de
authors.forename: Bruno
authors.initials: B
authors.lastname: Bulic
authors.forename: Marcus
authors.initials: M
authors.lastname: Pickhardt
authors.forename: Eckhard
authors.initials: E
authors.lastname: Mandelkow
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D016875:tau Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D016875:tau Proteins