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. 2023 Jan 19;18(2):121-137.
doi: 10.4103/1735-5362.367792. eCollection 2023 Apr.

Identifying potential ligand molecules EGFR mediated TNBC targeting the kinase domain-identification of customized drugs through in silico methods

Affiliations

Identifying potential ligand molecules EGFR mediated TNBC targeting the kinase domain-identification of customized drugs through VSports注册入口 - in silico methods

V体育2025版 - Hima Vyshnavi et al. Res Pharm Sci. .

"VSports手机版" Abstract

Background and purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer in which three hormone receptors are negative. This work aimed at identifying customized potential molecules inhibiting epidermal growth factor receptor (EGFR) by exploring variants using the pharmacogenomics approaches VSports手机版. .

Experimental approach: The pharmacogenomics approach has been followed to identify the genetic variants across the 1000 genomes continental population. Model proteins for the populations have been designed by including genetic variants in the reported positions. The 3D structures of the mutated proteins have been generated through homology modeling. The kinase domain present in the parent and the model protein molecules has been investigated. The docking study has been performed with the protein molecules against the kinase inhibitors evaluated by the molecular dynamic simulation studies. Molecular evolution has been performed to generate the potential derivatives of these kinase inhibitors suitable for the conserved region of the kinase domain. This study considered variants within the kinase domain as the sensitive region and remaining residues as the conserved region V体育安卓版. .

Findings/results: The results reveal that few kinase inhibitors interact with the sensitive region V体育ios版. Among the derivatives of these kinase inhibitors molecules, the potential kinase inhibitor that interacts with the different population models has been identified. .

Conclusions and implications: This study encompasses the importance of genetic variants in drug action as well as in the design of customized drugs VSports最新版本. This research gives way to designing customized potential molecules inhibiting EGFR by exploring variants using the pharmacogenomics approaches. .

Keywords: Conserved region; EGFR; Kinase domain; Sensitive region; TNBC V体育平台登录. .

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Conflict of interest statement

The authors declared no conflict of interest in this study.

Figures

Fig. 1
Fig. 1
1XKK with variants incorporated in its domain region.
Fig. 2
Fig. 2
The protein-drug interaction network of 4-aminoquinazoline derivatives and EGFR. EGFR, Epidermal growth factor receptor.
Fig. 3
Fig. 3
Ligand interaction diagram of complexes.
Fig. 4
Fig. 4
RMSD plot of ligand-target complexes during molecular dynamic simulation. RMSD, Root mean square deviation.
Fig. 5
Fig. 5
pIC50 v/s IC50 plot of kinase inhibitors.

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