Abstract
Epidermal growth factor receptors belong to the ErbB family of receptor tyrosine kinases (TKs) involved in the proliferation of normal and malignant cells. EGFR has attracted considerable attention as a target for cancer therapy. The findings reported herein are believed to provide some novel insights into the design of effective drugs for the therapeutic treatment of EGFR-related cancers. In particular, it is shown using sophisticated computational tools in a systematic way that the affinity of a wide spectrum of thiazolo[4,5-d]pyrimidine analogs can be carefully tuned up by seeking the desired goal in the structural modifications of EGFR, such as single point mutations of the critical EGFR residues in the active site. It is also demonstrated that a large number of the small ligand molecules can be efficiently divided into subgroups of the structurally similar ligands and that every such a subgroup has its unique inhibitory activity signature. The protein engineering approach, as quite reproducible, is proposed to be a viable partner to experiment in addressing a variety of issues, including investigation of clinically important mutations, development of drug resistance, identification of the most promising anti-cancer drug candidates, etc.
Keywords: Activity, affinity, binding energy, cancer, drug design, EGFR, molecular docking, inhibition, single point mutation.
Medicinal Chemistry
Title:Inhibitory Activity Against Epidermal Growth Factor Receptor (EGFR) Based on Single Point Mutations of Active Site Residues
Volume: 10 Issue: 3
Author(s): Petar M. Mitrasinovic
Affiliation:
Keywords: Activity, affinity, binding energy, cancer, drug design, EGFR, molecular docking, inhibition, single point mutation.
Abstract: Epidermal growth factor receptors belong to the ErbB family of receptor tyrosine kinases (TKs) involved in the proliferation of normal and malignant cells. EGFR has attracted considerable attention as a target for cancer therapy. The findings reported herein are believed to provide some novel insights into the design of effective drugs for the therapeutic treatment of EGFR-related cancers. In particular, it is shown using sophisticated computational tools in a systematic way that the affinity of a wide spectrum of thiazolo[4,5-d]pyrimidine analogs can be carefully tuned up by seeking the desired goal in the structural modifications of EGFR, such as single point mutations of the critical EGFR residues in the active site. It is also demonstrated that a large number of the small ligand molecules can be efficiently divided into subgroups of the structurally similar ligands and that every such a subgroup has its unique inhibitory activity signature. The protein engineering approach, as quite reproducible, is proposed to be a viable partner to experiment in addressing a variety of issues, including investigation of clinically important mutations, development of drug resistance, identification of the most promising anti-cancer drug candidates, etc.
Export Options
About this article
Cite this article as:
Mitrasinovic M. Petar, Inhibitory Activity Against Epidermal Growth Factor Receptor (EGFR) Based on Single Point Mutations of Active Site Residues, Medicinal Chemistry 2014; 10 (3) . https://dx.doi.org/10.2174/157340641003140304143442
DOI https://dx.doi.org/10.2174/157340641003140304143442 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
Related Articles
-
Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Exploring the Synthesis and Anticancer Potential of L-Tyrosine-Platinum(II) Hybrid Molecules
Medicinal Chemistry Matrix Metalloproteinase Inhibitors as Prospective Agents for the Prevention and Treatment of Cardiovascular and Neoplastic Diseases
Current Topics in Medicinal Chemistry Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias
Current Pharmaceutical Design Haploidentical Stem Cell Transplantation in Childhood
Current Cancer Therapy Reviews Anti-Mycobacterial Peroxides: A New Class of Agents for Development Against Tuberculosis
Medicinal Chemistry Endoglin-Targeted Cancer Therapy
Current Drug Delivery Editorial: Molecular Imaging of Protein and Peptide
Current Protein & Peptide Science The Clinical Utility of CA 19-9 in Pancreatic Adenocarcinoma: Diagnostic and Prognostic Updates
Current Molecular Medicine Cannabis-Derived Substances in Cancer Therapy – An Emerging Anti- Inflammatory Role for the Cannabinoids
Current Clinical Pharmacology Nutrition, Brain Aging, and Alzheimers Disease
Current Nutrition & Food Science Subject Index to Volume 4
Current Drug Targets Vascular Biomarkers in Asthma and COPD
Current Topics in Medicinal Chemistry Preclinical Toxicity of Paclitaxel Biopolymer Formulation
Anti-Cancer Agents in Medicinal Chemistry Clinical Applications of <sup>18</sup>F-FDG PET/CT in Monitoring Anti-cancer Therapies
Current Pharmaceutical Biotechnology Lectin Glycoarray Technologies for Nanoscale Biomedical Detection
Protein & Peptide Letters Antiplatelet and Anticoagulation Strategies in the Prevention and Treatment of Ischemic Stroke
Current Pharmaceutical Design The Impact of the Emerging Genomics Data on the Management of Agerelated Phenotypes in the Context of Cellular Senescence
Current Drug Targets In Vitro and In Vivo Antimetastatic Effects of ZSTK474 on Prostate Cancer DU145 Cells
Current Cancer Drug Targets Eph Receptors as Drug Targets: Single-Chain Antibodies and Beyond
Current Drug Targets