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Decoding dynamic interactions between EGFR-TKD and DAC through computational and experimental approaches

  • In the quest for effective lung cancer treatments, the potential of 3,6-diaminoacridine-9-carbonitrile (DAC) has emerged as a game changer. While DAC's efficacy against glioblastoma is well documented, its role in combating lung cancer has remained largely untapped. This study focuses on CTX-1, exploring its interaction with the pivotal EGFR-TKD protein, a crucial target in lung cancerIn the quest for effective lung cancer treatments, the potential of 3,6-diaminoacridine-9-carbonitrile (DAC) has emerged as a game changer. While DAC's efficacy against glioblastoma is well documented, its role in combating lung cancer has remained largely untapped. This study focuses on CTX-1, exploring its interaction with the pivotal EGFR-TKD protein, a crucial target in lung cancer therapeutics. A meticulous molecular docking analysis revealed that CTX-1 exhibits a noteworthy binding affinity of −7.9 kcal/mol, challenging Erlotinib, a conventional lung cancer medication, which displayed a binding affinity of −7.3 kcal/mol. For a deeper understanding of CTX-1's molecular mechanics, this study employed rigorous 100-ns molecular dynamics simulations, demonstrating CTX-1's remarkable stability in comparison with erlotinib. The Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) method further corroborated these results, with CTX-1 showing a free binding energy of −105.976 ± 1.916 kJ/mol. The true prowess of CTX-1 was tested against diverse lung cancer cell lines, including A549, Hop-62 and H-1299. CTX-1 not only significantly outperformed erlotinib in anticancer activity but also exhibited a spectrum of therapeutic effects. It effectively diminished cancer cell viability, induced DNA damage, halted cell cycle progression, generated reactive oxygen species (ROS), impaired mitochondrial transmembrane potential, instigated apoptosis and successfully inhibited EGFR-TKD. This study not only underscores the potential of CTX-1 a formidable contender in lung cancer treatment but also marks a paradigm shift in oncological therapeutics, offering new horizons in the fight against this formidable disease.show moreshow less

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Metadaten
Document Type:Article (reviewed)
Zitierlink: https://opus.hs-offenburg.de/10115
Bibliografische Angaben
Title (English):Decoding dynamic interactions between EGFR-TKD and DAC through computational and experimental approaches
Subtitle (English):A novelbreakthrough in lung melanoma treatment
Author:Rajesh Kumar Meher, Showkat Ahmad Mir, Kritika SinghStaff Member, Nobendu Mukerjee, Binata Nayak, Ajoy Kumer, Torki A. Zughaibi, Mohd Shahnawaz Khan, Shams Tabrez
Year of Publication:2024
Date of first Publication:2024/04/29
Place of publication:Hoboken
Publisher:John Wiley & Sons Ltd.
First Page:1
Last Page:20
Article Number:e18263
Parent Title (English):Journal of Cellular and Molecular Medicine
Volume:28
Issue:9
ISSN:1582-1838 (Print)
ISSN:1582-4934 (Online)
DOI:https://doi.org/10.1111/jcmm.18263
Language:English
Inhaltliche Informationen
Institutes:Fakultät Elektrotechnik, Medizintechnik und Informatik (EMI) (ab 04/2019)
Collections of the Offenburg University:Bibliografie
GND Keyword:Medizin
Tag:CTX-1; EGFR-TKD; ROS; cancer; erlotinib; lung cancer
Formale Angaben
Relevance for "Jahresbericht über Forschungsleistungen":Wiss. Zeitschriftenartikel reviewed: Listung in Master Journal List
Open Access: Open Access 
 Gold 
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International