Abstract
Colorectal cancer possesses the third highest diagnostic rate and is the second leading cause of cancer death in the USA as reported by NIH. Epidermal Growth Factor Receptor (EGFR), a transmembrane protein, participates in PLC gamma-1, RAS-RAF-MEK-MAPKs, phosphatidylinositol-3 kinase, Akt pathways and plays a key role in normal functioning of cell division, cell differentiation, apoptosis and migration. This protein is found to be overexpressed in more than 60% of the colorectal cancers. Overexpressed EGFR advances the tumorigenic properties through cell cycle dysregulation and activates signaling pathways linked to cancer such as WNT/β-catenin, transforming growth factor β (TGF-β) and phosphoinositide-3-kinase (PI3K). Inhibiting the overexpressed EGFR protein has been proposed for the treatment and many inhibitors have been reported suppressing the activity of EGFR. However, patients in malignant state of cancer show resistance to those inhibitors, which open a wide space to research for the discovery of novel inhibitors. The present study employed Molecular Docking and Virtual Screening to find novel inhibitors with high affinity against EGFR. Molecular docking of existing inhibitors resulted in the compound titled as BGB-283 (PubChem CID-89670174) having the highest score, which was subjected to similarity search to retrieve the drugs with similar structure. The virtual screening concluded a compound SCHEMBL18435602 (PubChem CID-126517400) which revealed a better affinity with the target protein. A comparative study of both the compounds showed equivalent pharmacokinetic properties. These identified drugs have a high potential to act as EGFR inhibitors and can show promising results in the research of colorectal cancer.
Keywords: Colorectal cancer, EGFR, ADMET, Virtual screening, Molecular docking, APC.
Current Topics in Medicinal Chemistry
Title:An In Silico Investigation of Potential EGFR Inhibitors for the Clinical Treatment of Colorectal Cancer
Volume: 18 Issue: 27
Author(s): Manisha Majhi, Meer Asif Ali, Akanksha Limaye, Kritika Sinha, Praveena Bairagi, Megha Chouksey, Ruchi Shukla, Nisha Kanwar, Tajamul Hussain, Anuraj Nayarisseri*Sanjeev Kumar Singh*
Affiliation:
- In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh,India
- Center of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh,Saudi Arabia
Keywords: Colorectal cancer, EGFR, ADMET, Virtual screening, Molecular docking, APC.
Abstract: Colorectal cancer possesses the third highest diagnostic rate and is the second leading cause of cancer death in the USA as reported by NIH. Epidermal Growth Factor Receptor (EGFR), a transmembrane protein, participates in PLC gamma-1, RAS-RAF-MEK-MAPKs, phosphatidylinositol-3 kinase, Akt pathways and plays a key role in normal functioning of cell division, cell differentiation, apoptosis and migration. This protein is found to be overexpressed in more than 60% of the colorectal cancers. Overexpressed EGFR advances the tumorigenic properties through cell cycle dysregulation and activates signaling pathways linked to cancer such as WNT/β-catenin, transforming growth factor β (TGF-β) and phosphoinositide-3-kinase (PI3K). Inhibiting the overexpressed EGFR protein has been proposed for the treatment and many inhibitors have been reported suppressing the activity of EGFR. However, patients in malignant state of cancer show resistance to those inhibitors, which open a wide space to research for the discovery of novel inhibitors. The present study employed Molecular Docking and Virtual Screening to find novel inhibitors with high affinity against EGFR. Molecular docking of existing inhibitors resulted in the compound titled as BGB-283 (PubChem CID-89670174) having the highest score, which was subjected to similarity search to retrieve the drugs with similar structure. The virtual screening concluded a compound SCHEMBL18435602 (PubChem CID-126517400) which revealed a better affinity with the target protein. A comparative study of both the compounds showed equivalent pharmacokinetic properties. These identified drugs have a high potential to act as EGFR inhibitors and can show promising results in the research of colorectal cancer.
Export Options
About this article
Cite this article as:
Majhi Manisha, Ali Asif Meer , Limaye Akanksha , Sinha Kritika , Bairagi Praveena , Chouksey Megha , Shukla Ruchi, Kanwar Nisha , Hussain Tajamul , Nayarisseri Anuraj *, Singh Kumar Sanjeev *, An In Silico Investigation of Potential EGFR Inhibitors for the Clinical Treatment of Colorectal Cancer, Current Topics in Medicinal Chemistry 2018; 18 (27) . https://dx.doi.org/10.2174/1568026619666181129144107
DOI https://dx.doi.org/10.2174/1568026619666181129144107 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Metabolomic Heterogeneity of Urogenital Tract Cancers Analyzed by Complementary Chromatographic Techniques Coupled with Mass Spectrometry
Current Medicinal Chemistry Nanoparticles for Colorectal Cancer Targeted Drug Delivery and MR Imaging: Current Situation and Perspectives
Current Cancer Drug Targets Targeted Therapies in Head and Neck Cancer: Past, Present and Future
Reviews on Recent Clinical Trials The Type II Transmembrane Serine Protease, Matriptase-2: Possible Links to Cancer?
Anti-Cancer Agents in Medicinal Chemistry The Need for Improvement of the Treatment of Advanced and Metastatic Cervical Cancer, the Rationale for Combined Chemo-Immunotherapy
Anti-Cancer Agents in Medicinal Chemistry Past, Present and Future of Targeted Therapy in Solid Tumors
Current Cancer Drug Targets Molecular Replacement in Cancer Therapy: Reversing Cancer Metabolic and Mitochondrial Dysfunction, Fatigue and the Adverse Effects of Cancer Therapy
Current Cancer Therapy Reviews Base Excision Repair, the Redox Environment and Therapeutic Implications
Current Molecular Pharmacology Curcumin Targets in Inflammation and Cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases
Current Molecular Pharmacology Comparative Analysis of Current Modality of Therapy in Head and Neck Squamous Cell Carcinoma Correlating the Expression Level of p38α
Current Cancer Therapy Reviews Tissue-Specific Therapeutic Targeting of p53 in Cancer: One Size Does Not Fit All
Current Pharmaceutical Design Studies on the Biotransformations and Biodistributions of Metal-Containing Drugs Using X-Ray Absorption Spectroscopy
Current Topics in Medicinal Chemistry Recent Advances in Predicting Protein Classification and Their Applications to Drug Development
Current Topics in Medicinal Chemistry Targeting RhoA/Rho Kinase and p21-Activated Kinase Signaling to Prevent Cancer Development and Progression
Recent Patents on Anti-Cancer Drug Discovery Autumn Royal and Egnatia Grape Extracts Differently Modulate Cell Proliferation in Human Colorectal Cancer Cells
Endocrine, Metabolic & Immune Disorders - Drug Targets Computational and Experimental Approaches for Modeling Gene Regulatory Networks
Current Pharmaceutical Design The Engaged Role of Tumor Microenvironment in Cancer Metabolism: Focusing on Cancer-Associated Fibroblast and Exosome Mediators
Anti-Cancer Agents in Medicinal Chemistry Anti-Angiogenic Therapy as a Cancer Treatment Paradigm
Current Medicinal Chemistry - Anti-Cancer Agents Prediction and Analysis of Hepatocellular Carcinoma Related Genes Using Gene Ontology and KEGG
Current Bioinformatics