Publications [#330223] of Michael J. Therien

Papers Published

1. Isabel, E; Bateman, KP; Chauret, N; Cromlish, W; Desmarais, S; Duong, LT; Falgueyret, J-P; Gauthier, JY; Lamontagne, S; Lau, CK; Léger, S; LeRiche, T; Lévesque, J-F; Li, CS; Massé, F; McKay, DJ; Mellon, C; Nicoll-Griffith, DA; Oballa, RM; Percival, MD; Riendeau, D; Robichaud, J; Rodan, GA; Rodan, SB; Seto, C; Thérien, M; Truong, VL; Wesolowski, G; Young, RN; Zamboni, R; Black, WC, The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor., Bioorganic & medicinal chemistry letters, vol. 20 no. 3 (February, 2010), pp. 887-892 [doi]
   (last updated on 2026/01/18)

   Abstract:
   MK-0674 is a potent and selective cathepsin K inhibitor from the same structural class as odanacatib with a comparable inhibitory potency profile against Cat K. It is orally bioavailable and exhibits long half-life in pre-clinical species. In vivo studies using deuterated MK-0674 show stereoselective epimerization of the alcohol stereocenter via an oxidation/reduction cycle. From in vitro incubations, two metabolites could be identified: the hydroxyleucine and the glucuronide conjugate which were confirmed using authentic synthetic standards.