Abstract
There were many hurdles in the drug discovery of cathepsin K inhibitors such as species differences not only in bone metabolism but also in amino acid sequences in the critical site of the target enzyme, discrepancies between PK/PD due to unique tissue distribution of the inhibitor affecting both efficacy and side effects originated from a characteristic intracellular or tissue distribution of some classes of compounds. The value of this new therapeutic approach over the launched indirect competitors should be further clarified from the efficacy and side effect point of view. The cathepsin K inhibitor drug discovery was initiated based on a strong and osteoclast-specific expression of this enzyme. However, the tissues and cells expressing cathepsin K have been expanding as the investigation on pathological conditions progressed with respect to side effects as well as new possible indications.
Keywords: Cathepsin K inhibitors, Species differences, PK/PD, On- and Off-target Side Effects, Osteoporosis, Bone resorption, Osteoclasts
Current Topics in Medicinal Chemistry
Title: Hurdles in the Drug Discovery of Cathepsin K Inhibitors
Volume: 10 Issue: 7
Author(s): Motohiko Kometani, Kazuhiko Nonomura, Takashi Tomoo and Satoru Niwa
Affiliation:
Keywords: Cathepsin K inhibitors, Species differences, PK/PD, On- and Off-target Side Effects, Osteoporosis, Bone resorption, Osteoclasts
Abstract: There were many hurdles in the drug discovery of cathepsin K inhibitors such as species differences not only in bone metabolism but also in amino acid sequences in the critical site of the target enzyme, discrepancies between PK/PD due to unique tissue distribution of the inhibitor affecting both efficacy and side effects originated from a characteristic intracellular or tissue distribution of some classes of compounds. The value of this new therapeutic approach over the launched indirect competitors should be further clarified from the efficacy and side effect point of view. The cathepsin K inhibitor drug discovery was initiated based on a strong and osteoclast-specific expression of this enzyme. However, the tissues and cells expressing cathepsin K have been expanding as the investigation on pathological conditions progressed with respect to side effects as well as new possible indications.
Export Options
About this article
Cite this article as:
Kometani Motohiko, Nonomura Kazuhiko, Tomoo Takashi and Niwa Satoru, Hurdles in the Drug Discovery of Cathepsin K Inhibitors, Current Topics in Medicinal Chemistry 2010; 10 (7) . https://dx.doi.org/10.2174/156802610791113478
DOI https://dx.doi.org/10.2174/156802610791113478 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- 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
-
Recombinant Antibodies in Cancer Therapy
Current Protein & Peptide Science Invasive Aspergillosis: New Insights into Disease, Diagnostic and Treatment
Current Pharmaceutical Design Identification of L-Amino Acid Oxidase (Mb-LAAO) with Antibacterial Activity in the Venom of Montivipera bornmuelleri, a Viper from Lebanon
Infectious Disorders - Drug Targets Evaluation of Endothelial (dys)Function, Left Ventricular Structure and Function in Patients with Chronic Kidney Disease
Current Vascular Pharmacology Extracellular Matrix Remodeling in Hypertension
Current Hypertension Reviews Proniosomes in Transdermal Drug Delivery
Current Pharmaceutical Design Pharmacogenetics of Statins Therapy
Recent Patents on Cardiovascular Drug Discovery Pulmonary Hypertension: Clinical Presentation, Diagnosis, Treatment,and Dana Point World Symposium Highlights
Current Respiratory Medicine Reviews Traumatic Brain Injury: Preclinical Imaging Diagnostic(s) and Therapeutic Approaches
Current Pharmaceutical Design Urocortin: Cardiovascular Actions and Therapeutic Implications
Letters in Drug Design & Discovery Treatment of Diabetic Foot Ulcers
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Nitric Oxide Signaling and the Cross Talk with Prostanoids Pathways in Vascular System
Medicinal Chemistry Heart Rate Variability Indexes in Dementia: A Systematic Review with a Quantitative Analysis
Current Alzheimer Research Cannabinoids as Neuroprotective Agents in Traumatic Brain Injury
Current Pharmaceutical Design Proteinase-Activated Receptor-2: Physiological and Pathophysiological Roles
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Cardiac Side Effects of Chemotherapy: State of Art and Strategies for a Correct Management
Current Vascular Pharmacology Immunosuppressive Therapy for Myelodysplastic Syndromes
Current Pharmaceutical Design Red Wine, Arterial Stiffness and Central Hemodynamics
Current Pharmaceutical Design Metal Complexes, their Cellular Targets and Potential for Cancer Therapy
Current Pharmaceutical Design Stress, Depression and Antidepressant Treatment Options in Patients Suffering from Multiple Sclerosis
Current Pharmaceutical Design