title: [Cathepsin K antagonists: preclinical and clinical data].
abstract: Cathepsin K, a cysteine protease, is an essential enzyme in degradation of collagen type I. Since cathepsin K is relatively specific to osteoclasts, it represents a promising candidate for drug development. In the past decades, efforts have been made in developing highly potent, selective and orally applicable cathepsin K inhibitors. In contrast to balicatib and relacatib, whose drug development programmes were stopped due to cutaneous side-effects related to limited drug specificity, the more specific cathepsin K inhibitors odanacatib (ODN) and ONO-5334 have entered clinical trials. Odanacatib progressively increases bone mineral density (BMD) and decreases bone resorption markers in postmenopausal women with low BMD. Its clinical efficacy and safety was confirmed by several clinical studies but indicates that odanacatib is characterized by a resolution-of-effect with increases in bone resorption and rapid decreases in BMD following treatment discontinuation. A phase III fracture prevention study in postmenopausal women with osteoporosis is currently in the final phase.
authors.affiliation: II. Medizinische Abteilung (Rheumatologie/Osteologie & Gastroenterologie), KH Barmherzige Schwestern, Akademisches Lehrkrankenhaus der MUW, 1060, Wien, Stumpergasse 13, Österreich, marion.gamsjaeger@bhs.at.
authors.forename: Marion
authors.initials: M
authors.lastname: Gamsjäger
authors.forename: Heinrich
authors.initials: H
authors.lastname: Resch
mesh_terms: D001713:Biphenyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy; D056657:Cathepsin K / Q000037:antagonists & inhibitors*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D010010:Osteoclasts / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D053778:Thiazolidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001713:Biphenyl Compounds; D050071:Bone Density Conservation Agents; C560865:ONO-5334; D053778:Thiazolidines; C534130:CTSK protein, human; D056657:Cathepsin K; C527128:odanacatib