ABSTRACT:
The Epidermal Growth Factor Receptor (EGFR) plays a pivotal role in the progression of various cancers and represents a well-established target for anticancer drug development. In the present study, a series of pyrazole derivatives were evaluated for their potential inhibitory activity against five EGFR kinase receptor variants using molecular docking simulations. The selected EGFR protein structures 4HJO, 5HG7, 5XDX, 6S9B and 6Z4B were retrieved from the Protein Data Bank and subjected to comparative docking analysis using AutoDock Vina. Among the tested receptors, 4HJO exhibited the most favourable binding affinities, with binding energies ranging from -10.9 to -9.7kcal/mol, and showed 1-2 hydrogen bonds with key amino acid residues. 5HG7 displayed binding energies between -10.1 to -8.9kcal/mol, also forming 1-2 hydrogen bonds. The docking scores for 5XDX ranged from -8.7 to -7.6kcal/mol, accompanied by 2-3 hydrogen bonds, while 6S9B demonstrated moderate binding energies from -9.1 to -8.2kcal/mol, with 2-3 hydrogen bonds. Notably, 6Z4B exhibited binding energies between -9.5 to -8.6kcal/mol, and formed 4-5 hydrogen bonds, indicating strong hydrogen bonding potential. The comparative analysis suggests that the binding efficiency and interaction profiles of pyrazole derivatives vary significantly across EGFR isoforms, with 4HJO and 6Z4B showing particularly promising results. These findings provide valuable insights into the structural preferences of EGFR-ligand interactions and support the further development of pyrazole-based compounds as potential EGFR-targeted anticancer agents.
Cite this article:
Rashmi T, Vinutha S. Targeting Epidermal Growth Factor Receptor (EGFR) Kinase variants with Pyrazole Derivatives: A Comparative Molecular Docking Study. Research Journal Pharmacy and Technology. 2026;19(6):2621-8. doi: 10.52711/0974-360X.2026.00375
Cite(Electronic):
Rashmi T, Vinutha S. Targeting Epidermal Growth Factor Receptor (EGFR) Kinase variants with Pyrazole Derivatives: A Comparative Molecular Docking Study. Research Journal Pharmacy and Technology. 2026;19(6):2621-8. doi: 10.52711/0974-360X.2026.00375 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2026-19-6-32
REFERENCES:
1. Anita S. Godase, Nayana V. Pimpodkar and Yogita Indalkar R. An Overview on A Pyrazole: Promising Moiety. Asian J Pharm Tech. 2015; 5(4): 201-213.
2. Balaji PN, Prathusha K, Chandu TJ, Sai Sreevani M, Johnsi Rani P and Harini P. Synthesis, Characterization and Antimicrobial Activity of Some Synthesized Isoxazole and Pyrazole Derivatives. Asian J Research Chem. 2011; 4(2): 301-303.
3. Shantaram G. Khanage, Popat Mohite B and Appala Raju S. Synthesis, Anticancer and Antibacterial Activity of Some Novel 1, 2, 4-Triazole Derivatives Containing Pyrazole and Tetrazole Rings. Asian J Research Chem. 2011; 4(4): 567-573.
4. Panneer Selvam T, Saravanan G, Prakash CR and Dinesh Kumar P. Microwave-Assisted Synthesis, Characterization and Biological Activity of Novel Pyrazole Derivatives. Asian J Pharm Res. 2011; 1(4): 126-129.
5. Alhamaky SM, Khalil NA, Bass AK, Osama N and Hassan MS. Design, Synthesis, Docking Studies and Investigation of Dual EGFR/VEGFR‐2 Inhibitory Potentials of New Pyrazole and Pyrazolopyridine Derivatives. Drug Development Research. 2025; 86(1): 70056-60.
6. Raghu MS, Kumar CP, Prashanth MK, Kumar KY, Prathibha BS, Kanthimathi G, Alissa SA, Alghulikah HA and Osman SM. Novel 1, 3, 5-triazine-based pyrazole derivatives as potential antitumor agents and EFGR kinase inhibitors: Synthesis, cytotoxicity, DNA binding, molecular docking and DFT studies. New Journal of Chemistry. 2021; 45(31): 13909-24.
7. Ashok Gadre G, Nawathye VV, Dalavi DB, Upadhyaya DJ, Thorat BR and Yamgar RS. Synthesis and Characterization of Hydrazones, Pyrazoles and Pyrazolones from 8-Amino-6-Chloro Coumarine. Asian J Research Chem. 2011; 4(10): 1621-1624.
8. Sherbiny FF, Bayoumi AH, El-Morsy AM, Sobhy M, and Hagras M. Design, Synthesis, biological Evaluation and molecular docking studies of novel Pyrazolo [3, 4-d] Pyrimidine derivative scaffolds as potent EGFR inhibitors and cell apoptosis inducers. Bioorganic Chemistry. 2021; 116(1): 105325-29.
9. Khalilullah H, Agarwal DK, Ahsan MJ, Jadav SS, Mohammed HA, Khan MA, Mohammed SA and Khan R. Synthesis and anti-cancer activity of new pyrazolinyl-indole derivatives: pharmacophoric interactions and docking studies for identifying new EGFR inhibitors. International Journal of Molecular Sciences. 2022; 23(12): 6548-52.
10. Ahmed MF, Santali EY, El-Deen EM, Naguib IA and El-Haggar R. Development of pyridazine derivatives as potential EGFR inhibitors and apoptosis inducers: Design, synthesis, anticancer evaluation and molecular modeling studies. Bioorganic Chemistry. 2021; 106(1): 104473-77.
11. Abdullahi SH, Uzairu A, Shallangwa GA, Uba S and Umar AB. 2D and 3D-QSAR Modeling of 1H Pyrazole Derivatives as EGFR Inhibitors: Molecular Docking and Pharmacokinetic Profiling. Chemistry Africa. 2023; 6(3): 1381-98.
12. Silvia P, Ongko J and Antonius Y. Epidermal growth factor receptor mutant T790M-L858R-V948R inhibitor from Calophyllum inophyllum L. leaf as potential non-small cell lung cancer drugs. Journal of Pharmacy and Pharmacognosy Research. 2024; 12(5): 881-91.
13. Al-Muntaser SM, Al-Karmalawy AA, El-Naggar AM, Ali AK, Abd El-Sattar NE and Abbass EM. Novel 4-thiophenyl-pyrazole, pyridine, and pyrimidine derivatives as potential antitumor candidates targeting both EGFR and VEGFR-2; design, synthesis, biological evaluations, and in silico studies. RSC advances. 2023; 13(18): 12184-203.
14. Govindarao K, Srinivasan N, Suresh R, Raheja RK, Annadurai S, Bhandare RR and Shaik AB. Quinoline conjugated 2-azetidinone derivatives as prospective anti-breast cancer agents: In-vitro antiproliferative and anti-EGFR activities, molecular docking and in-silico drug likeliness studies. Journal of Saudi Chemical Society. 2022; 26(3): 101471-74.
15. Sepay N, Mondal R, Al-Muhanna MK and Saha D. Identification of natural flavonoids as novel EGFR inhibitors using DFT, molecular docking, and molecular dynamics. New Journal of Chemistry. 2022; 46(20): 9735-44.
16. Vishwajit Patil S and Prithviraj Patil A. Molecular Docking: A useful approach of Drug Discovery on the Basis of their Structure. Asian Journal of Pharmaceutical Research. 2023; 13(3): 191-5.
17. Soham Pawar, Chaitrali Kulkarni, Puja Gadade, Supriya Pujari, Surajkumar Kakade, Rohane SH and Redasani VK. Molecular Docking using different Tools. Asian Journal of Pharmaceutical Research. 2023; 13(4): 292-6.
18. Payal Nagrale R, Payal Gadiwan S, Nitin Gorad Y, Omkar Lahamge D, Omkar Kanse P, Omkar Veer M and Rinaj Attar. Overview of Tools used in Molecular Docking. Asian Journal of Pharmaceutical Research. 2024; 14(3): 326-30.
19. Bhaskar Dawane S, Baseer M Shaikh, Namdev Khandare T, Gajanan Mandawad G, Santosh Chobe S and Shankaraiah Konda G. Synthesis of Some Novel Substituted Pyrazole Based Chalcones and Their In-Vitro Antimicrobial Activity. Asian J Research Chem. 2010; 3(1): 90-93.
20. Vijay Kumar Tirlapur and Kashinath Noubade. Synthesis, Characterization and Biological Activities of New Pyrimidines and Pyrazoles Derivative. Asian J Research Chem. 2010; 3(3): 659-662.