title: The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K.
abstract: Odanacatib is a potent, selective, and neutral cathepsin K inhibitor which was developed to address the metabolic liabilities of the Cat K inhibitor L-873724. Substituting P1 and modifying the P2 side chain led to a metabolically robust inhibitor with a long half-life in preclinical species. Odanacatib was more selective in whole cell assays than the published Cat K inhibitors balicatib and relacatib. Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors.
authors.affiliation: Merck Frosst Centre for Therapeutic Research, 16711 TransCanada Hwy, Kirkland, Que., Canada.
authors.forename: Jacques Yves
authors.initials: JY
authors.lastname: Gauthier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chauret
authors.forename: Wanda
authors.initials: W
authors.lastname: Cromlish
authors.forename: Sylvie
authors.initials: S
authors.lastname: Desmarais
authors.forename: Le T
authors.initials: LT
authors.lastname: Duong
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Falgueyret
authors.forename: Donald B
authors.initials: DB
authors.lastname: Kimmel
authors.forename: Sonia
authors.initials: S
authors.lastname: Lamontagne
authors.forename: Serge
authors.initials: S
authors.lastname: Léger
authors.forename: Tammy
authors.initials: T
authors.lastname: LeRiche
authors.forename: Chun Sing
authors.initials: CS
authors.lastname: Li
authors.forename: Frédéric
authors.initials: F
authors.lastname: Massé
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: McKay
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nicoll-Griffith
authors.forename: Renata M
authors.initials: RM
authors.lastname: Oballa
authors.forename: James T
authors.initials: JT
authors.lastname: Palmer
authors.forename: M David
authors.initials: MD
authors.lastname: Percival
authors.forename: Denis
authors.initials: D
authors.lastname: Riendeau
authors.forename: Joel
authors.initials: J
authors.lastname: Robichaud
authors.forename: Gideon A
authors.initials: GA
authors.lastname: Rodan
authors.forename: Sevgi B
authors.initials: SB
authors.lastname: Rodan
authors.forename: Carmai
authors.initials: C
authors.lastname: Seto
authors.forename: Michel
authors.initials: M
authors.lastname: Thérien
authors.forename: Vouy-Linh
authors.initials: VL
authors.lastname: Truong
authors.forename: Michael C
authors.initials: MC
authors.lastname: Venuti
authors.forename: Gregg
authors.initials: G
authors.lastname: Wesolowski
authors.forename: Robert N
authors.initials: RN
authors.lastname: Young
authors.forename: Robert
authors.initials: R
authors.lastname: Zamboni
authors.forename: W Cameron
authors.initials: WC
authors.lastname: Black
mesh_terms: D000818:Animals; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003094:Collagen / Q000187:drug effects / Q000276:immunology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D012867:Skin / Q000166:cytology; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001381:Azepines; D001713:Biphenyl Compounds; D015853:Cysteine Proteinase Inhibitors; C527129:L-873724; D013450:Sulfones; D003094:Collagen; C509706:relacatib; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C527128:odanacatib