Abstract
Aberrant angiogenesis has been observed in many solid tumors. The formation and metastases of tumors such as non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) are very complex, often regulated by proangiogenic factors such as the vascular endothelial growth factor (VEGF) and other tyrosine kinases. The VEGFR, EGFR and mTOR pathways have played critical roles in controlling cell proliferation and angiogenesis. This paper reviews the mechanism and binding modes of recently approved tyrosine kinase inhibitors (TKIs), such as gefitinib, erlotinib, nilotinib, dasatinib, sunitinib, sorafenib, pazopanib, lapatinib, afinitor, and temsirolimus. We also cover the progresses of the recent development of tyrosine kinase inhibitors that are currently in the clinical trials at the phases I, II, and III, targeting the VEGFR, EGFR and/or mTOR pathways. Combination therapy intended to overcome drug resistance is also discussed. Recent TKI design based on the activation loop and the “DFG” conformation, is also discussed.
Keywords: Vandetanib, cediranib, motesanib, axitinib, vatalanib, SU5416, BIBF1120, AEE788, tandutinib, linifanib, dovitinib, telatinib, regorafenib, E7080, XL880, brivanib, tivozanib, ponatinib
Current Topics in Medicinal Chemistry
Title: Recent Advances in Small Molecule Inhibitors of VEGFR and EGFR Signaling Pathways
Volume: 11 Issue: 12
Author(s): Haizhen Zhong and J. Phillip Bowen
Affiliation:
Keywords: Vandetanib, cediranib, motesanib, axitinib, vatalanib, SU5416, BIBF1120, AEE788, tandutinib, linifanib, dovitinib, telatinib, regorafenib, E7080, XL880, brivanib, tivozanib, ponatinib
Abstract: Aberrant angiogenesis has been observed in many solid tumors. The formation and metastases of tumors such as non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) are very complex, often regulated by proangiogenic factors such as the vascular endothelial growth factor (VEGF) and other tyrosine kinases. The VEGFR, EGFR and mTOR pathways have played critical roles in controlling cell proliferation and angiogenesis. This paper reviews the mechanism and binding modes of recently approved tyrosine kinase inhibitors (TKIs), such as gefitinib, erlotinib, nilotinib, dasatinib, sunitinib, sorafenib, pazopanib, lapatinib, afinitor, and temsirolimus. We also cover the progresses of the recent development of tyrosine kinase inhibitors that are currently in the clinical trials at the phases I, II, and III, targeting the VEGFR, EGFR and/or mTOR pathways. Combination therapy intended to overcome drug resistance is also discussed. Recent TKI design based on the activation loop and the “DFG” conformation, is also discussed.
Export Options
About this article
Cite this article as:
Zhong Haizhen and Phillip Bowen J., Recent Advances in Small Molecule Inhibitors of VEGFR and EGFR Signaling Pathways, Current Topics in Medicinal Chemistry 2011; 11 (12) . https://dx.doi.org/10.2174/156802611795860924
DOI https://dx.doi.org/10.2174/156802611795860924 |
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
-
Unmet Needs in Ovarian Cancer: Dividing Histologic Subtypes to Exploit Novel Targets and Pathways
Current Cancer Drug Targets Minimally Invasive Surgery for Uterine Fibroids with Contained Tissue Extraction
Current Women`s Health Reviews Cardiotoxicity of Molecularly Targeted Agents
Current Cardiology Reviews Novel Insights Into the Role of MicroRNA in Lung Cancer Resistance to Treatment and Targeted Therapy
Current Cancer Drug Targets Genetic Predisposition to Parkinson’s Disease and Cancer
Current Cancer Drug Targets 18F-Labeled Proteins
Current Pharmaceutical Biotechnology Chemotherapy and Targeted Agents for Elderly Women with Advanced Breast Cancer
Recent Patents on Anti-Cancer Drug Discovery Synthesis of Quinazolines as Tyrosine Kinase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry PPARγ: Potential Therapeutic Target for Ailments Beyond Diabetes and its Natural Agonism
Current Drug Targets In Vitro Regulatory Effect of Epididymal Serpin CRES on Protease Activity of Proprotein Convertase PC4/PCSK4
Current Molecular Medicine A Promising Anti-Cancer and Anti-Oxidant Agents Based on the Pyrrole and Fused Pyrrole: Synthesis, Docking Studies and Biological Evaluation
Anti-Cancer Agents in Medicinal Chemistry The HOX Genes Network in Uro-Genital Cancers: Mechanisms and Potential Therapeutic Implications
Current Medicinal Chemistry Formulation and Characterization of Rutin Loaded Chitosan-alginate Nanoparticles: Antidiabetic and Cytotoxicity Studies
Current Drug Delivery Lipoxygenase Inhibitors for Cancer Prevention: Promises and Risks
Current Pharmaceutical Design Translational Research in Oncology: The Need of Additional In Vitro Preclinical Testing Methods for New Drugs
Current Pharmaceutical Design Modulating Co-Stimulation During Antigen Presentation to Enhance Cancer Immunotherapy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Recent Advances in the Research and Development of B-Raf Inhibitors
Current Medicinal Chemistry The Anti-Tumor Mechanism and Target of Triptolide Based on Network Pharmacology and Molecular Docking
Recent Patents on Anti-Cancer Drug Discovery Integrin αvβ3 Antagonists for Anti-Angiogenic Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Post-Translational Control of Sp-Family Transcription Factors
Current Genomics