Icotinib, Almonertinib, and Olmutinib: A 2D Similarity/Docking-Based Study to Predict the Potential Binding Modes and Interactions into EGFR

Faisal A Almalki; Ahmed M Shawky; Ashraf N Abdalla; Ahmed M Gouda

doi:10.3390/molecules26216423

Icotinib, Almonertinib, and Olmutinib: A 2D Similarity/Docking-Based Study to Predict the Potential Binding Modes and Interactions into EGFR

Molecules. 2021 Oct 24;26(21):6423. doi: 10.3390/molecules26216423.

Authors

Faisal A Almalki¹, Ahmed M Shawky^{2

3}, Ashraf N Abdalla^{4

5}, Ahmed M Gouda⁶

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
² Science and Technology Unit (STU), Umm Al-Qura University, Makkah 21955, Saudi Arabia.
³ Central Laboratory for Micro-analysis, Minia University, Minia 61519, Egypt.
⁴ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
⁵ Department of Pharmacology and Toxicology, Medicinal And Aromatic Plants Research Institute, National Center for Research, Khartoum 2404, Sudan.
⁶ Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.

Abstract

In the current study, a 2D similarity/docking-based study was used to predict the potential binding modes of icotinib, almonertinib, and olmutinib into EGFR. The similarity search of icotinib, almonertinib, and olmutinib against a database of 154 EGFR ligands revealed the highest similarity scores with erlotinib (0.9333), osimertinib (0.9487), and WZ4003 (0.8421), respectively. In addition, the results of the docking study of the three drugs into EGFR revealed high binding free energies (ΔG_b = -6.32 to -8.42 kcal/mol) compared to the co-crystallized ligands (ΔG_b = -7.03 to -8.07 kcal/mol). Analysis of the top-scoring poses of the three drugs was done to identify their potential binding modes. The distances between Cys797 in EGFR and the Michael acceptor sites in almonertinib and olmutinib were determined. In conclusion, the results could provide insights into the potential binding characteristics of the three drugs into EGFR which could help in the design of new more potent analogs.

Keywords: almonertinib; docking; icotinib; olmutinib; similarity search.

MeSH terms

Acrylamides / chemistry
Acrylamides / pharmacology*
Binding Sites / drug effects
Crown Ethers / chemistry
Crown Ethers / pharmacology*
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / metabolism
Humans
Indoles / chemistry
Indoles / pharmacology*
Ligands
Molecular Docking Simulation*
Molecular Structure
Piperazines / chemistry
Piperazines / pharmacology*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Quinazolines / chemistry
Quinazolines / pharmacology*

Substances

Acrylamides
Crown Ethers
Indoles
Ligands
Piperazines
Protein Kinase Inhibitors
Pyrimidines
Quinazolines
icotinib
olmutinib
EGFR protein, human
ErbB Receptors
aumolertinib

Grants and funding

19-MED-1-01-0001/Deanship of Scientific Research at Umm Al-Qura University, Mekkah, KSA