Abstract
Benzimidazole is a common kinase inhibitor scaffold and benzimidazole-based compounds interact with enzymes by multiple binding modes. In some cases, the benzimidazole acts as part of the hinge-binding motif, in others it has a scaffolding role without evidence for direct hinge binding. Several of these compounds are ATP-competitive inhibitors and show high selectivity by exploiting unique structural properties that distinguish one kinase from the majority of other kinases. However, the high specificity for a single target is not always sufficient. Thus another approach, called multi-target therapy, has been developed over the last few years. The simultaneous inhibition of various kinases may be useful because the disease is attacked at several relevant targets. Moreover, if a kinase becomes drug-resistant, a multitargeted drug can act on the other kinases. Some benzimidazole derivatives are multi-target inhibitors. In this article benzimidazole inhibitors are reported with their mechanisms of action, structure-activity relationship (SAR) and biological properties.
Keywords: ATP-competitive, benzimidazole, biological activity, kinase inhibition, multi-target inhibitor, SAR, selectivity.
Current Medicinal Chemistry
Title:Benzimidazole Derivatives as Kinase Inhibitors
Volume: 21 Issue: 20
Author(s): Laura Garuti, Marinella Roberti and Giovanni Bottegoni
Affiliation:
Keywords: ATP-competitive, benzimidazole, biological activity, kinase inhibition, multi-target inhibitor, SAR, selectivity.
Abstract: Benzimidazole is a common kinase inhibitor scaffold and benzimidazole-based compounds interact with enzymes by multiple binding modes. In some cases, the benzimidazole acts as part of the hinge-binding motif, in others it has a scaffolding role without evidence for direct hinge binding. Several of these compounds are ATP-competitive inhibitors and show high selectivity by exploiting unique structural properties that distinguish one kinase from the majority of other kinases. However, the high specificity for a single target is not always sufficient. Thus another approach, called multi-target therapy, has been developed over the last few years. The simultaneous inhibition of various kinases may be useful because the disease is attacked at several relevant targets. Moreover, if a kinase becomes drug-resistant, a multitargeted drug can act on the other kinases. Some benzimidazole derivatives are multi-target inhibitors. In this article benzimidazole inhibitors are reported with their mechanisms of action, structure-activity relationship (SAR) and biological properties.
Export Options
About this article
Cite this article as:
Garuti Laura, Roberti Marinella and Bottegoni Giovanni, Benzimidazole Derivatives as Kinase Inhibitors, Current Medicinal Chemistry 2014; 21 (20) . https://dx.doi.org/10.2174/0929867321666140217105714
DOI https://dx.doi.org/10.2174/0929867321666140217105714 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Novel Targets for Apoptosis Modulation: BAG3 Protein and Other Co- Chaperones
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Targeted Drug Delivery for Breast Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Oxidative Stress, Endothelial Dysfunction and Atherosclerosis
Current Pharmaceutical Design Advances of Paclitaxel Formulations Based on Nanosystem Delivery Technology
Mini-Reviews in Medicinal Chemistry From Multiple PAR1 Receptor/Protein Interactions to their Multiple Therapeutic Implications
Current Topics in Medicinal Chemistry Click Chemistry Based Functionalizations of Nucleoside, Nucleotide and Nucleic Acids
Current Organic Chemistry Subject Index To Volume 7
Current Drug Targets Meet Our Editorial Board Member
Current Medicinal Chemistry Polyphenols and Depression: from Chemistry to Medicine
Current Pharmaceutical Biotechnology Pluripotent Stem Cells for Livestock Health and Production
Current Stem Cell Research & Therapy AG490 Promotes HIF-1α Accumulation by Inhibiting Its Hydroxylation
Current Medicinal Chemistry The Characteristics, Functions and Inhibitors of Three Aminopeptidases Belonging to the M1 Family
Current Protein & Peptide Science Fibrates in the Chemical Action of Daunorubicin
Current Cancer Drug Targets Synthesis and Antitumor Activity of Novel N-Benzoyl-N'-substituted Pyrimidinyl (Thio)semicarbazide Derivatives
Letters in Drug Design & Discovery The Effect of Protein Restriction in the In Vitro Metabolism of Albendazole in Rats
Drug Metabolism Letters Synthesis and Bioactivity of (R)-Ricinoleic Acid Derivatives: A Review
Current Medicinal Chemistry Role of Erlotinib in Influencing the Quality of Life of Cancer Patients
Clinical Cancer Drugs Therapeutic Effect of Ribbon-Type Nuclear Factor-κB Decoy Oligonucleotides in a Rat Model of Inflammatory Bowel Disease
Current Gene Therapy Targets for Anti-metastatic Drug Development
Current Pharmaceutical Design RepurposeVS: A Drug Repurposing-Focused Computational Method for Accurate Drug-Target Signature Predictions
Combinatorial Chemistry & High Throughput Screening