Abstract
The limitations of many mono-kinase inhibitors can be overcome by agents with multi-target action. An important advantage of targeting more than one kinase, is an increase in potency, due to the synergistic effect. Moreover, this approach can reduce the possibility of developing drug resistance. Several multitarget agents have been designed as single kinase inhibitors and found to be multi-target inhibitors because of the structural homology among the ATP-binding site of kinases. In other cases, these inhibitors have been obtained by optimization of potent individual inhibitors or by combination of selective ligands. Also some irreversible inhibitors act on different kinases and covalently modify the cysteine residues located near the ATP-binding pocket. In this review the most recent examples of multi-kinase inhibitors are reported, focusing on chemical structures, structure-activity relationship (SAR) and biological activity. These inhibitors, suitably substituted, could be used in designing other multitarget agents. Virtual molecular docking would suggest potential targets of molecules, moreover combining pharmacophore combination and screening methods could probably help in the discovery of more potent multikinase inhibitors.
Keywords: ATP-competitive, biological activity, heterocycles, inhibition, irreversible inhibitors, kinase, multi-target, SAR.
Current Medicinal Chemistry
Title:Multi-Kinase Inhibitors
Volume: 22 Issue: 6
Author(s): Laura Garuti, Marinella Roberti and Giovanni Bottegoni
Affiliation:
Keywords: ATP-competitive, biological activity, heterocycles, inhibition, irreversible inhibitors, kinase, multi-target, SAR.
Abstract: The limitations of many mono-kinase inhibitors can be overcome by agents with multi-target action. An important advantage of targeting more than one kinase, is an increase in potency, due to the synergistic effect. Moreover, this approach can reduce the possibility of developing drug resistance. Several multitarget agents have been designed as single kinase inhibitors and found to be multi-target inhibitors because of the structural homology among the ATP-binding site of kinases. In other cases, these inhibitors have been obtained by optimization of potent individual inhibitors or by combination of selective ligands. Also some irreversible inhibitors act on different kinases and covalently modify the cysteine residues located near the ATP-binding pocket. In this review the most recent examples of multi-kinase inhibitors are reported, focusing on chemical structures, structure-activity relationship (SAR) and biological activity. These inhibitors, suitably substituted, could be used in designing other multitarget agents. Virtual molecular docking would suggest potential targets of molecules, moreover combining pharmacophore combination and screening methods could probably help in the discovery of more potent multikinase inhibitors.
Export Options
About this article
Cite this article as:
Garuti Laura, Roberti Marinella and Bottegoni Giovanni, Multi-Kinase Inhibitors, Current Medicinal Chemistry 2015; 22 (6) . https://dx.doi.org/10.2174/0929867321666141216125528
DOI https://dx.doi.org/10.2174/0929867321666141216125528 |
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
-
A Systematic Review of Selected Musculoskeletal Late Effects in Survivors of Childhood Cancer
Current Pediatric Reviews Protein Phosphatase 1 and Its Complexes in Carcinogenesis
Current Cancer Drug Targets Transcription Factors as Molecular Targets: Molecular Mechanisms of Decoy ODN and their Design
Current Drug Targets Microenvironmental Regulation of Cancer Stem Cell Phenotypes
Current Stem Cell Research & Therapy Epigenetic Therapies of Cancer
Current Cancer Therapy Reviews Employing New Cellular Therapeutic Targets for Alzheimers Disease: A Change for the Better?
Current Neurovascular Research Blocking Ca2+ Entry: A Way to Control Cell Proliferation
Current Medicinal Chemistry Prostaglandin J2 Family and the Cardiovascular System
Current Vascular Pharmacology Oligonucleotide-based Gene Therapy for Cardiovascular Disease Are Oligonucleotide Therapeutics Novel Cardiovascular Drugs
Current Drug Targets Differential Binding Preference of Methylpheophorbide a and Its Diboronated Derivatives to Albumin and Low Density Lipoproteins
Anti-Cancer Agents in Medicinal Chemistry Role of the Retinoblastoma Tumor Suppressor in the Maintenance of Genome Integrity
Current Molecular Medicine The Mechanism of Calcitriol in Cancer Prevention and Treatment
Current Medicinal Chemistry Altering the Sphingosine-1-Phosphate/Ceramide Balance: A Promising Approach for Tumor Therapy
Current Pharmaceutical Design Ras-Induced Senescence and its Physiological Relevance in Cancer
Current Cancer Drug Targets Anti-Apoptotic Genes in the Survival of Monocytic Cells During Infection
Current Genomics Novel and Emerging Drugs for Acute Myeloid Leukemia: Pharmacology and Therapeutic Activity
Current Medicinal Chemistry Lumiflavin Enhances the Effects of Ionising Radiation on Ovarian Cancer Stem-Like Cells by Inhibiting Autophagy
Anti-Cancer Agents in Medicinal Chemistry New Ways to Improve Breast Cancer Therapy Targeting Specific Molecular Pathways
Current Cancer Therapy Reviews Lysine Acetyltransferases CBP and p300 as Therapeutic Targets in Cognitive and Neurodegenerative Disorders
Current Pharmaceutical Design Expression and Functions of Heat Shock Proteins in the Normal and Pathological Mammalian Eye
Current Molecular Medicine