Genomic and computational-aided integrative drug repositioning strategy for EGFR and ROS1 mutated NSCLC

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F24%3A00597670" target="_blank" >RIV/86652036:_____/24:00597670 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S1567576924012037?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1567576924012037?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.intimp.2024.112682" target="_blank" >10.1016/j.intimp.2024.112682</a>

Result language

angličtina

Original language name

Genomic and computational-aided integrative drug repositioning strategy for EGFR and ROS1 mutated NSCLC

Original language description

Non-small cell lung cancer (NSCLC) has been marked as the major cause of death in lung cancer patients. Due to tumor heterogeneity, mutation burden, and emerging resistance against the available therapies in NSCLC, it has been posing potential challenges in the therapy development. Hence, identification of cancer-driving mutations and their effective inhibition have been advocated as a potential approach in NSCLC treatment. Thereof, this study aims to employ the genomic and computational-aided integrative drug repositioning strategy to identify the potential mutations in the selected molecular targets and repurpose FDA-approved drugs against them. Accordingly, molecular targets and their mutations, i.e., EGFR (V843L, L858R, L861Q, and P1019L) and ROS1 (G1969E, F2046Y, Y2092C, and V2144I), were identified based on TCGA dataset analysis. Following, virtual screening and redocking analysis, Elbasvir, Ledipasvir, and Lomitapide drugs for EGFR mutants (>-10.8 kcal/ mol) while Indinavir, Ledipasvir, Lomitapide, Monteleukast, and Isavuconazonium for ROS1 mutants (>-8.8 kcal/mol) were found as putative inhibitors. Furthermore, classical molecular dynamics simulation and endpoint binding energy calculation support the considerable stability of the selected docked complexes aided by substantial hydrogen bonding and hydrophobic interactions in comparison to the respective control complexes. Conclusively, the repositioned FDA-approved drugs might be beneficial alone or in synergy to overcome acquired resistance to EGFR and ROS1-positive lung cancers.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30102 - Immunology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Immunopharmacology

ISSN

1567-5769

e-ISSN

1878-1705

Volume of the periodical

139

Issue of the periodical within the volume

SEP 30 2024

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

22

Pages from-to

112682

UT code for WoS article

001278062500001

EID of the result in the Scopus database

2-s2.0-85198717651