Cathepsin K Inhibition: A New Mechanism for the Treatment of Osteoporosis

Calcified Tissue International
Le T DuongBente Langdahl

Abstract

Cathepsin K (CatK), a cysteine protease, is highly expressed by osteoclasts and very efficiently degrades type I collagen, the major component of the organic bone matrix. Robust genetic and pharmacological preclinical studies consistently demonstrate that CatK inhibition increases bone mass, improves bone microarchitecture and strength. Recent advances in the understanding of the molecular and cellular mechanisms involved in bone modeling and remodeling suggest that inhibition of CatK decreases bone resorption, but increases the number of cells of osteoclast lineage. This in turn maintains the signals for bone formation, and perhaps may even increase bone formation on some cortical surfaces. Several CatK inhibitors, including relacatib, balicatib, odanacatib and ONO-5334 had entered clinical development for metabolic bone disorders with increased bone resorption, such as postmenopausal osteoporosis. However, odanacatib (ODN) is the only candidate continuing in development. ODN is a highly selective oral CatK inhibitor dosed once-weekly in humans. In a Phase 2 clinical trial, postmenopausal women treated with ODN had sustained reductions of bone resorption markers, while bone formation markers returned to normal after an initial...Continue Reading

References

Feb 2, 1995·The New England Journal of Medicine·S C Manolagas, R L Jilka
May 11, 1999·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·T HiranoJ M Hock
Sep 22, 1999·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·N HoC Francomano
Jul 20, 2002·Current Molecular Medicine·Gabriela Motyckova, David E Fisher
May 7, 2005·Advanced Drug Delivery Reviews·Yoshiyuki YasudaDieter Brömme
Oct 26, 2005·Bone·Cosimo Roberto RussoLuigi Ferrucci
May 4, 2007·The New England Journal of Medicine·Dennis M BlackUNKNOWN HORIZON Pivotal Fracture Trial
Jan 30, 2008·Bioorganic & Medicinal Chemistry Letters·Jacques Yves GauthierW Cameron Black
Feb 28, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Pascale ChavassieuxPierre D Delmas
May 29, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Barbara M Obermayer-PietschUNKNOWN EUROFORS Investigators
Apr 25, 2009·Expert Opinion on Investigational Drugs·Dieter Brömme, Fabien Lecaille
Aug 13, 2009·The New England Journal of Medicine·Steven R CummingsUNKNOWN FREEDOM Trial
Feb 4, 2010·Nature Reviews. Rheumatology·Nicholas HarveyCyrus Cooper
Aug 25, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Brenda L PennypackerDonald B Kimmel
Aug 27, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·John A EismanAntonio Lombardi
Dec 15, 2010·Bone·Roland BaronR Graham G Russell
Feb 4, 2011·The Journal of Clinical Endocrinology and Metabolism·Henry G BoneJ Christopher Gallagher
Feb 10, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Shreyasee AminSundeep Khosla
Feb 11, 2011·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·C JeromeR Gamse
Mar 23, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kelem KassahunKenneth Koeplinger
May 17, 2011·Journal of the American Academy of Dermatology·Thomas M RüngerVanessa Smith
Nov 25, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Patricia J MasarachiaLe T Duong
Nov 25, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Tara CusickLe T Duong
Nov 25, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Socrates PapapoulosHenry G Bone
Dec 14, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Dennis M BlackRichard Eastell
Feb 7, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Hai QingLynda F Bonewald
Jul 11, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Bente LangdahlAlbert Leung
Jan 17, 2013·The Journal of Clinical Investigation·Sutada LotinunRoland Baron
Jan 23, 2013·The Journal of Clinical Endocrinology and Metabolism·Kim BrixenAnne E de Papp
May 24, 2013·Calcified Tissue International·Kim HenriksenT John Martin
May 30, 2013·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·T NakamuraS Uchida

❮ Previous
Next ❯

Citations

Apr 24, 2016·Biochemical Pharmacology·Kakoli Mukherjee, Naibedya Chattopadhyay
Nov 5, 2016·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Ronit MaromBrendan Lee
Nov 12, 2016·Nature Reviews. Drug Discovery·Yasuko OnoHiroyuki Sorimachi
Nov 20, 2016·FEBS Letters·Marko NovinecBrigita Lenarčič
May 4, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Jun LuGe Zhang
Jul 27, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Preety PanwarDieter Brömme
Dec 2, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Bente L Langdahl, Stuart H Ralston
Oct 27, 2017·Archives of Disease in Childhood·Claire Louise Wood, S Faisal Ahmed
Aug 24, 2018·PLoS Neglected Tropical Diseases·Jair L Siqueira-NetoPhilip J Rosenthal
Jan 22, 2019·British Journal of Clinical Pharmacology·Julie A StoneS Aubrey Stoch
May 22, 2019·The Journal of Clinical Investigation·Sutada LotinunRoland Baron
Sep 4, 2019·Nature Reviews. Drug Discovery·Srinivasa Reddy BonamSylviane Muller
Mar 25, 2017·Frontiers in Endocrinology·Toshihiro Sugiyama, Hiromi Oda
Jun 21, 2017·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Melisa Bunderson-SchelvanRaymond F Hamilton
Apr 19, 2018·Analytical Cellular Pathology (Amsterdam)·Hideki KitauraWei-Ren Shen
May 8, 2018·Medicinal Research Reviews·Harshika AwasthiAtul Gupta
Nov 30, 2018·Physiological Research·I Zofkova, P Nemcikova
Mar 9, 2017·Drugs·Edoardo MarraniRolando Cimaz
Jan 14, 2021·Scientific Reports·Yoko Miyazaki-AsatoJunro Yamashita
Feb 13, 2021·Journal of Personalized Medicine·Nithya Subrahmanyam, Hamidreza Ghandehari
Mar 17, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Socrates PapapoulosArthur Santora
May 4, 2021·Frontiers in Pharmacology·Xiaoyan CaiChanghai Ding
Jul 31, 2021·Frontiers in Cell and Developmental Biology·Áron PánczélAttila Mócsai

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2021 Meta ULC. All rights reserved