Abstract
Cathepsin K is a cysteine protease that plays an important role in the pathological process of bone resorption. Selective cathepsin K inhibitors may thus provide great potential in the treatment of osteoporosis. Pharmaceutical interest in this area is highlighted by the rising number of publications and patent applications. Most recently, the interim results of three clinical trials conducted by Novartis, GlaxoSmithKline, and Merck have strengthened the validation of the target for the therapeutic intervention of osteoporosis. Here we report a series of Cbz-leucyl-(4-piperidinylphenyl)aminoethyl amides based on dipeptidyl anilines for cathepsin K inhibition. These new non-covalent inhibitors exhibit single digit nM inhibition of the cathepsin family. Molecular modeling studies on the interactions responsible for the potency of these inhibitors for cathepsin K will be also discussed.
Keywords: Non-covalent, cathepsin, inhibitor
Current Topics in Medicinal Chemistry
Title: Non-Covalent Cathepsin K Inhibitors for the Treatment of Osteoporosis
Volume: 6 Issue: 4
Author(s): Tae-Seong Kim and Andrew S. Tasker
Affiliation:
Keywords: Non-covalent, cathepsin, inhibitor
Abstract: Cathepsin K is a cysteine protease that plays an important role in the pathological process of bone resorption. Selective cathepsin K inhibitors may thus provide great potential in the treatment of osteoporosis. Pharmaceutical interest in this area is highlighted by the rising number of publications and patent applications. Most recently, the interim results of three clinical trials conducted by Novartis, GlaxoSmithKline, and Merck have strengthened the validation of the target for the therapeutic intervention of osteoporosis. Here we report a series of Cbz-leucyl-(4-piperidinylphenyl)aminoethyl amides based on dipeptidyl anilines for cathepsin K inhibition. These new non-covalent inhibitors exhibit single digit nM inhibition of the cathepsin family. Molecular modeling studies on the interactions responsible for the potency of these inhibitors for cathepsin K will be also discussed.
Export Options
About this article
Cite this article as:
Kim Tae-Seong and Tasker S. Andrew, Non-Covalent Cathepsin K Inhibitors for the Treatment of Osteoporosis, Current Topics in Medicinal Chemistry 2006; 6 (4) . https://dx.doi.org/10.2174/156802606776287036
DOI https://dx.doi.org/10.2174/156802606776287036 |
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
-
Anti-Inflammatory and Anti-Allergy Drugs in Rhinosinusitis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Carbonic Anhydrase Inhibition/Activation: Trip of a Scientist Around the World in the Search of Novel Chemotypes and Drug Targets
Current Pharmaceutical Design Editorial [Hot Topic: Metabolic Syndrome in an Asian Chinese Population and Agents and Targets for Cardiovascular Protection (Guest Editors: M.L. Fung and T.M. Wong)]
Cardiovascular & Hematological Disorders-Drug Targets Human- and Virus-Encoded microRNAs as Potential Targets of Antiviral Therapy
Mini-Reviews in Medicinal Chemistry Recent Insights into Therapeutic Potential of Plant-Derived Flavonoids against Cancer
Anti-Cancer Agents in Medicinal Chemistry Evaluation of Online Grocery Platform Alternatives Using Fuzzy ZNumbers
Journal of Fuzzy Logic and Modeling in Engineering Pharmacokinetics of Drugs in Neonates: Pattern Recognition Beyond Compound Specific Observations
Current Pharmaceutical Design Estrogenic Compounds, Estrogen Receptors and Vascular Cell Signaling in the Aging Blood Vessels
Current Medicinal Chemistry Modulation of the TRPV1 Channel: Current Clinical Trials and Recent Patents with Focus on Neurological Conditions
Recent Patents on CNS Drug Discovery (Discontinued) Inhibitors of the Lipid Phosphatase SHIP2 Discovered by High Throughput Affinity Selection-Mass Spectrometry Screening of Combinatorial Libraries
Combinatorial Chemistry & High Throughput Screening Primary Tumors of the Sacrum: Imaging Findings
Current Medical Imaging Pharmacological Intervention at CCR1 and CCR5 as an Approach for Cancer: Help or Hindrance
Current Topics in Medicinal Chemistry Unsupervised End-to-End Brain Tumor Magnetic Resonance Image Registration Using RBCNN: Rigid Transformation, B-Spline Transformation and Convolutional Neural Network
Current Medical Imaging Fluorescence- and Spin-Labeled Carbonic Anhydrase Inhibitors
Current Pharmaceutical Design Synthesis and Biological Activity of Substituted-4,5,6,7-tetrahydrothieno Pyridines: A Review
Mini-Reviews in Medicinal Chemistry Synthetic Attempts Towards Eminent Anti-viral Candidates of SARS-CoV
Mini-Reviews in Medicinal Chemistry Comparative Molecular Surface Analysis (CoMSA) for Virtual Combinatorial Library Screening of Styrylquinoline HIV-1 Blocking Agents
Combinatorial Chemistry & High Throughput Screening Preface
Central Nervous System Agents in Medicinal Chemistry Newly Emergent 2019-nCoV and New Uses of an Old Medicine, Doxycycline; A Hypothesis.
Infectious Disorders - Drug Targets Meet Our Editorial Board Member
Current Medicinal Chemistry