Abstract
Oncogenic B-Raf has been identified in a variety of cancers with high incidence, especially in malignant melanoma and thyroid cancer. Most B-Raf mutations elicit elevated kinase activity and the constitutive activation of Ras/Raf/MEK/ERK pathway, which induces proliferation and promotes malignant transformation. Therefore, B-Raf inhibitors, targeting B-Raf or mutated B-Raf, have received increasing momentum in oncology drug discovery arena. This review focuses on the diverse small-molecule inhibitors of B-Raf kinase recently reported in the literature, including those currently in clinical and preclinical phase. They are described as two categories, type I or type II kinase inhibitors, based on their different mechanism of action with active or inactive conformations of the B-Raf kinase derived from the available crystal structures or molecular docking analysis. A particular emphasis is placed on their binding modes and the structure-activity relationship (SAR) of each chemical structure class.
Keywords: B-Raf, B-RafV600E, B-Raf kinase inhibitors, binding mode, SAR, mechanism of action
Current Medicinal Chemistry
Title: Recent Advances in the Research and Development of B-Raf Inhibitors
Volume: 17 Issue: 16
Author(s): Hui-Fang Li, Yadong Chen, Sha-Sha Rao, Xiu-Mei Chen, Hai-Chun Liu, Ji-Hong Qin, Wei-Fang Tang, Yue-Wang, Xiang Zhou and Tao Lu
Affiliation:
Keywords: B-Raf, B-RafV600E, B-Raf kinase inhibitors, binding mode, SAR, mechanism of action
Abstract: Oncogenic B-Raf has been identified in a variety of cancers with high incidence, especially in malignant melanoma and thyroid cancer. Most B-Raf mutations elicit elevated kinase activity and the constitutive activation of Ras/Raf/MEK/ERK pathway, which induces proliferation and promotes malignant transformation. Therefore, B-Raf inhibitors, targeting B-Raf or mutated B-Raf, have received increasing momentum in oncology drug discovery arena. This review focuses on the diverse small-molecule inhibitors of B-Raf kinase recently reported in the literature, including those currently in clinical and preclinical phase. They are described as two categories, type I or type II kinase inhibitors, based on their different mechanism of action with active or inactive conformations of the B-Raf kinase derived from the available crystal structures or molecular docking analysis. A particular emphasis is placed on their binding modes and the structure-activity relationship (SAR) of each chemical structure class.
Export Options
About this article
Cite this article as:
Li Hui-Fang, Chen Yadong, Rao Sha-Sha, Chen Xiu-Mei, Liu Hai-Chun, Qin Ji-Hong, Tang Wei-Fang, Yue-Wang , Zhou Xiang and Lu Tao, Recent Advances in the Research and Development of B-Raf Inhibitors, Current Medicinal Chemistry 2010; 17 (16) . https://dx.doi.org/10.2174/092986710791111242
DOI https://dx.doi.org/10.2174/092986710791111242 |
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
-
Apoptosis Imaging to Monitor Cancer Therapy: The Road to Fast Treatment Evaluation?
Current Pharmaceutical Biotechnology Speciation of Metal Complexes of Medicinal Interest: Relationship between Solution Equilibria and Pharmaceutical Properties
Current Medicinal Chemistry The Flavin-Containing Monoooxygenases (FMOs): Genetic Variation and its Consequences for the Metabolism of Therapeutic Drugs
Current Pharmacogenomics Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier
Current Pharmaceutical Design Novel Therapeutic Approaches to Regulate Human Dihydrofolate Reductase Activity and Expression
Current Enzyme Inhibition Magnetic Resonance Imaging of Uncommon Hepatic Mesenchymal Tumours: Haemangioendothelioma and Angiosarcoma
Current Medical Imaging “Cancer Antigen WT1 Protein-Derived Peptide”-Based Treatment of Cancer -Toward the Further Development
Current Medicinal Chemistry Amyloidogenicity of p53: A Hidden Link Between Protein Misfolding and Cancer
Current Protein & Peptide Science Withdrawal Notice: Drug Repurposing for Prospective Anti-Cancer Agents Along with the Clinical Status of the Repurposed Drug
Anti-Cancer Agents in Medicinal Chemistry Preclinical Toxicity of Paclitaxel Biopolymer Formulation
Anti-Cancer Agents in Medicinal Chemistry Contribution of Catecholamine Reactive Intermediates and Oxidative Stress to the Pathologic Features of Heart Diseases
Current Medicinal Chemistry PPARγ in Angiogenesis and Vascular Development
Current Angiogenesis (Discontinued) Recent Advances in the Synthesis and Anticancer Activity of Some Molecules Other Than Nitrogen Containing Heterocyclic Moeities
Mini-Reviews in Medicinal Chemistry Impact of Oncogenic Protein Tyrosine Phosphatases in Cancer
Anti-Cancer Agents in Medicinal Chemistry Targeting Leptin as a Therapeutic Strategy against Ovarian Cancer Peritoneal Metastasis
Anti-Cancer Agents in Medicinal Chemistry An Optimised Radiolabel Procedure to Prepare 99mTc-Colloidal Rhenium Sulphide to Improve Radiochemical Purity
Current Radiopharmaceuticals Pro- and Anti-Arrhythmic Effects of Anti-Inflammatory Drugs
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry New Therapeutic Approaches to Liver Fibrosis: A Practicable Route?
Current Medicinal Chemistry Cancer-associated Autoantibodies as Biomarkers for Early Detection and Prognosis is Cancer: An Update
Current Cancer Therapy Reviews Patent Selections
Recent Patents on Anti-Cancer Drug Discovery