Structural Insight and Development of EGFR Tyrosine Kinase Inhibitors

Lung cancer has a high prevalence, with a growing number of new cases and mortality every year. Furthermore, the survival rate of patients with non-small-cell lung carcinoma (NSCLC) is still quite low in the majority of cases. Despite the use of conventional therapy such as tyrosine kinase inhibitor...

Full description

Saved in:
Bibliographic Details
Published in:Molecules Vol. 27; no. 3; p. 819
Main Authors: Amelia, Tasia, Kartasasmita, Rahmana Emran, Ohwada, Tomohiko, Tjahjono, Daryono Hadi
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 26.01.2022
MDPI
Subjects:
activation
Amino acids
Animals
Apoptosis
binding
Binding sites
Carcinoma, Non-Small-Cell Lung
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - metabolism
Drug Design
Drug Discovery
EGFR
Epidermal growth factor
ErbB Receptors
ErbB Receptors - antagonists & inhibitors
ErbB Receptors - chemistry
ErbB Receptors - metabolism
Humans
Hydrogen bonds
inhibitor
kinase
Kinases
Ligands
Lung Neoplasms
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Models, Molecular
Mutation
Organic chemistry
Phosphorylation
Protein Conformation
Protein Conformation - drug effects
Protein Kinase Inhibitors
Protein Kinase Inhibitors - chemistry
Protein Kinase Inhibitors - pharmacology
Proteins
QD241-441
Review
binding
kinase
inhibitor
activation
EGFR
ISSN:1420-3049, 1420-3049
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Lung cancer has a high prevalence, with a growing number of new cases and mortality every year. Furthermore, the survival rate of patients with non-small-cell lung carcinoma (NSCLC) is still quite low in the majority of cases. Despite the use of conventional therapy such as tyrosine kinase inhibitor for Epidermal Growth Factor Receptor (EGFR), which is highly expressed in most NSCLC cases, there was still no substantial improvement in patient survival. This is due to the drug’s ineffectiveness and high rate of resistance among individuals with mutant EGFR. Therefore, the development of new inhibitors is urgently needed. Understanding the EGFR structure, including its kinase domain and other parts of the protein, and its activation mechanism can accelerate the discovery of novel compounds targeting this protein. This study described the structure of the extracellular, transmembrane, and intracellular domains of EGFR. This was carried out along with identifying the binding pose of commercially available inhibitors in the ATP-binding and allosteric sites, thereby clarifying the research gaps that can be filled. The binding mechanism of inhibitors that have been used clinically was also explained, thereby aiding the structure-based development of new drugs.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
ObjectType-Review-3
content type line 23
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27030819