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The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K.
Gauthier JY,
Chauret N,
Cromlish W,
Desmarais S,
Duong le T,
Falgueyret JP,
Kimmel DB,
Lamontagne S,
Léger S,
LeRiche T,
Li CS,
Massé F,
McKay DJ,
Nicoll-Griffith DA,
Oballa RM,
Palmer JT,
Percival MD,
Riendeau D,
Robichaud J,
Rodan GA,
Rodan SB,
Seto C,
Thérien M,
Truong VL,
Venuti MC,
Wesolowski G,
Young RN,
Zamboni R,
Black WC.
Merck Frosst Centre for Therapeutic Research, 16711 TransCanada Hwy, Kirkland, Que., Canada.
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.
PMID: 18226527 [PubMed - indexed for MEDLINE]
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