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Journals / Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi / 2026 / Cilt: 42 Sayı: 2

Molecular Docking Analysis of Quinazoline Derivatives Against EGFR Tyrosine Kinase: An In Silico Study Comparative with Erlotinib

EGFR Tirozin Kinazına Karşı Kinazolin Türevlerinin Moleküler Docking Analizi: Erlotinib ile Karşılaştırmalı In Silico Bir Çalışma

Medine Karadağ Alpaslan(ONDOKUZ MAYIS UNIVERSITY, SCHOOL OF MEDICINE)0000-0002-9115-275X
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Publication Date
2026-06-26
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AI Summary & Key Takeaways

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⚡ TL;DR(Too Long; Didn't Read)

Conclusion: These findings indicate that quinazoline derivatives have potential as EGFR inhibitors, and compound CID:24945791, in particular, could be a strong candidate.

📌 3 Key Takeaways

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Objective & Hypothesis:Background/Aim: Cancer is one of the leading causes of morbidity and mortality worldwide.
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Key Findings & Data:Methods: In this study, the binding potential of three quinazoline compounds (CID: 24945791, 1474881, and 14022362) selected from the PubChem database to the EGFR tyrosine kinase domain was evaluated using molecular docking, and the results were compared with those of the reference inhibitor Erlotinib.
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Conclusion & Impact:Conclusion: These findings indicate that quinazoline derivatives have potential as EGFR inhibitors, and compound CID:24945791, in particular, could be a strong candidate.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:EGFR · Moleküler Docking · Kinazolin Türevleri

Abstract

Background/Aim: Cancer is one of the leading causes of morbidity and mortality worldwide. Epidermal growth factor receptor (EGFR) is attracting attention as an important therapeutic target in many types of cancer. The aim of this study is to evaluate the binding affinity and interaction profiles of selected quinazoline derivatives against the EGFR tyrosine kinase domain using molecular docking analysis. Methods: In this study, the binding potential of three quinazoline compounds (CID: 24945791, 1474881, and 14022362) selected from the PubChem database to the EGFR tyrosine kinase domain was evaluated using molecular docking, and the results were compared with those of the reference inhibitor Erlotinib. Results: According to the docking results, compound CID: 24945791 was determined as the ligand of the highest affinity, with a binding energy of -8.11 kcal/mol. The hydrogen bonds formed by this compound with PRO770 and MET769, the π-cation interaction with LYS721, and the intense π-alkyl interactions with hydrophobic amino acids significantly contribute to its binding stability. Compound CID:1474881 exhibits a moderate binding affinity with a binding energy of -7.32 kcal/mol and is stabilized in the active site by multiple hydrogen bonds and hydrophobic interactions. In contrast, compound CID:14022362 was identified as the ligand with the lowest affinity, with a binding energy of -5.67 kcal/mol, and the steric overlap observed with CYS751 negatively affected its binding stability. Conclusion: These findings indicate that quinazoline derivatives have potential as EGFR inhibitors, and compound CID:24945791, in particular, could be a strong candidate. This study provides an in silico basis for the development of next-generation EGFR inhibitors.

Özet

Arka Plan/Amaç: Kanser dünya genelinde morbidite ve mortalitenin başlıca nedenlerinden biridir. Epidermal büyüme faktörü reseptörü ise birçok kanser türünde önemli bir terapötik hedef olarak dikkat çekmektedir. Bu çalışmanın amacı, seçilen kinazolin türevlerinin EGFR tirozin kinaz domainine karşı bağlanma afinitesini ve etkileşim profillerini moleküler docking yöntemiyle değerlendirmektir. Yöntem: Bu çalışmada, PubChem veri tabanından seçilen ve kinazolin çekirdeği içeren üç farklı bileşiğin (CID: 24945791, 1474881 ve 14022362) EGFR tirozin kinaz domainine bağlanma potansiyeli, referans inhibitör Erlotinib ile karşılaştırılmalı şekilde moleküler docking yöntemi kullanılarak değerlendirilmiştir. Bulgular: Docking sonuçlarına göre CID: 24945791 bileşiği -8.11 kcal/mol bağlanma enerjisi ile en yüksek afiniteli ligand olarak belirlenmiştir. Bu bileşiğin PRO770 ve MET769 ile oluşturduğu hidrojen bağları, LYS721 ile π-katyon etkileşimi ve hidrofobik amino asitlerle kurduğu yoğun π-alkil etkileşimleri, bağlanma stabilitesine önemli katkılar sağlamaktadır. CID:1474881 bileşiği -7.32 kcal/mol bağlanma enerjisi ile orta düzeyde bir bağlanma afinitesi gösterirken, çoklu hidrojen bağı ve hidrofobik etkileşimler ile aktif bölgede stabilize olmuştur. Buna karşılık, CID: 14022362 bileşiği -5.67 kcal/mol bağlanma enerjisi ile en düşük afiniteli ligand olarak belirlenmiş olup, CYS751 ile gözlenen sterik çakışma bağlanma stabilitesini olumsuz etkilemiştir. Sonuç: Elde edilen bulgular kinazolin türevlerinin EGFR inhibitörü olarak potansiyel taşıdığını ve özellikle CID: 24945791 bileşiğinin güçlü bir aday olabileceğini göstermektedir. Bu çalışma yeni nesil EGFR inhibitörlerinin geliştirilmesine yönelik in silico bir temel sunmaktadır.

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Cite This Article

Alpaslan, M. K. (2026). Molecular Docking Analysis of Quinazoline Derivatives Against EGFR Tyrosine Kinase: An In Silico Study Comparative with Erlotinib. Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi, Cilt: 42 Sayı: 2. https://doi.org/10.65520/erciyesfen.1927513

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