Abstract
Cathepsin K (Cat K) is the primary enzyme involved in Type I collagen degradation in bone resorption. The development of a Cat K inhibitor should provide an effective treatment for osteoporosis. Key components of a clinically viable inhibitor are oral bioavailability, high selectivity over related cathepsins, and a covalent, reversible warhead to bind to the active site cysteine of the enzyme. This article reviews recent advances in the design of inhibitors derived from peptidic leads that contain either a ketone or nitrile electrophile. Three of these compounds have progressed into clinical trials and one, odanacatib (5), is currently in Phase III studies for the treatment of post-menopausal osteoporosis.
Keywords: Osteoporosis, cathepsin K, cysteine protease, lysosomotropism, selective inhibitor, peptidomimetic, bone resorption
Current Topics in Medicinal Chemistry
Title: Peptidomimetic Inhibitors of Cathepsin K
Volume: 10 Issue: 7
Author(s): W. Cameron Black
Affiliation:
Keywords: Osteoporosis, cathepsin K, cysteine protease, lysosomotropism, selective inhibitor, peptidomimetic, bone resorption
Abstract: Cathepsin K (Cat K) is the primary enzyme involved in Type I collagen degradation in bone resorption. The development of a Cat K inhibitor should provide an effective treatment for osteoporosis. Key components of a clinically viable inhibitor are oral bioavailability, high selectivity over related cathepsins, and a covalent, reversible warhead to bind to the active site cysteine of the enzyme. This article reviews recent advances in the design of inhibitors derived from peptidic leads that contain either a ketone or nitrile electrophile. Three of these compounds have progressed into clinical trials and one, odanacatib (5), is currently in Phase III studies for the treatment of post-menopausal osteoporosis.
Export Options
About this article
Cite this article as:
Cameron Black W., Peptidomimetic Inhibitors of Cathepsin K, Current Topics in Medicinal Chemistry 2010; 10 (7) . https://dx.doi.org/10.2174/156802610791113450
DOI https://dx.doi.org/10.2174/156802610791113450 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Immunoadsorption Therapy for Patients with Dilated Cardiomyopathy and Heart Failure
Current Cardiology Reviews ACE2 and Diabetic Complications
Current Pharmaceutical Design Targeting ErbB3: the New RTK(id) on the Prostate Cancer Block
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Combinations Against Combinations: Associations of Anti-HIV 1 Reverse Transcriptase Drugs Challenged by Constellations of Drug Resistance Mutations
Current Drug Metabolism Angiogenesis as a therapeutic target in breast cancer
Mini-Reviews in Medicinal Chemistry Induced Pluripotent Stem Cell Technology: A Paradigm Shift in Medical Science for Drug Screening and Disease Modeling
Current Medicinal Chemistry B-Type Natriuretic Peptide for Diagnosis and Therapy
Recent Patents on Cardiovascular Drug Discovery Kawasakis Disease, Acrodynia, and Mercury
Current Medicinal Chemistry Kinins and Cardiovascular Diseases
Current Pharmaceutical Design Antimicrobial Agents-Associated with QT Interval Prolongation
Current Drug Safety The Electrocardiographic Manifestations of Arrhythmogenic Right Ventricular Dysplasia
Current Cardiology Reviews Calcium Ions in Inherited Cardiomyopathies
Medicinal Chemistry By Discontinuing Beta-Blockers Before an Exercise Test, We may Precipitate a Rebound Phenomenon
Current Vascular Pharmacology Aldose Reductase: A Novel Target for Cardioprotective Interventions
Current Drug Targets Mesenchymal Stem Cells as a Source of Dopaminergic Neurons: A Potential Cell Based Therapy for Parkinson's Disease
Current Stem Cell Research & Therapy Targeting Transient Receptor Potential Channels in Cardiometabolic Diseases and Myocardial Ischemia Reperfusion Injury
Current Drug Targets The CD4C/HIVNef Transgenic Model of AIDS
Current HIV Research Recreational Drug Misuse and Stroke
Current Drug Abuse Reviews TakoTsubo Cardiomyopathy A Short Review
Current Cardiology Reviews The Pathophysiology of Heart Failure in Children: The Basics
Current Cardiology Reviews