title: Discovery of novel aspartyl ketone dipeptides as potent and selective caspase-3 inhibitors.
abstract: The discovery of a series of potent, selective and reversible dipeptidyl caspase-3 inhibitors are reported. The iterative discovery process of using combinatorial chemistry, parallel synthesis, moleculare modelling and structural biology will be discussed.
authors.affiliation: Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada & Co, PO Box 1005, Pointe-Claire-Dorval, Québec, Canada H9R 4P8. yongxin_han@merck.com
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Han
authors.forename: André
authors.initials: A
authors.lastname: Giroux
authors.forename: Erich L
authors.initials: EL
authors.lastname: Grimm
authors.forename: Renée
authors.initials: R
authors.lastname: Aspiotis
authors.forename: Sébastien
authors.initials: S
authors.lastname: Francoeur
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Bayly
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Mckay
authors.forename: Sophie
authors.initials: S
authors.lastname: Roy
authors.forename: Steve
authors.initials: S
authors.lastname: Xanthoudakis
authors.forename: John P
authors.initials: JP
authors.lastname: Vaillancourt
authors.forename: Dita M
authors.initials: DM
authors.lastname: Rasper
authors.forename: John
authors.initials: J
authors.lastname: Tam
authors.forename: Paul
authors.initials: P
authors.lastname: Tawa
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Thornberry
authors.forename: Erin P
authors.initials: EP
authors.lastname: Paterson
authors.forename: Margarita
authors.initials: M
authors.lastname: Garcia-Calvo
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Becker
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rotonda
authors.forename: Donald W
authors.initials: DW
authors.lastname: Nicholson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Zamboni
mesh_terms: D001224:Aspartic Acid / Q000737:chemistry*; D001665:Binding Sites; D053148:Caspase 3; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D020650:Combinatorial Chemistry Techniques; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D061945:Caspase Inhibitors; D004151:Dipeptides; D004791:Enzyme Inhibitors; D007659:Ketones; D001224:Aspartic Acid; C505407:CASP3 protein, human; D053148:Caspase 3