Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
Science and Technology Unit (STU), Umm Al-Qura University, Makkah 21955, Saudi Arabia.
Molecules. 2021 Oct 24;26(21):6423. doi: 10.3390/molecules26216423.
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 (Δ = -6.32 to -8.42 kcal/mol) compared to the co-crystallized ligands (Δ = -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.
在本研究中，采用二维相似性/对接研究预测了伊可替尼、阿美替尼和奥希替尼与 EGFR 的潜在结合模式。对 154 种 EGFR 配体数据库中的伊可替尼、阿美替尼和奥希替尼进行相似性搜索，结果与厄洛替尼（0.9333）、奥希替尼（0.9487）和 WZ4003（0.8421）的相似度得分最高。此外，将这三种药物对接进入 EGFR 的研究结果表明，与共结晶配体相比，它们具有较高的结合自由能（Δ = -6.32 至-8.42 kcal/mol）。对三种药物的最高得分构象进行分析，以确定它们的潜在结合模式。测定了 EGFR 中 Cys797 与阿美替尼和奥希替尼中迈克尔受体部位之间的距离。总之，这些结果可以深入了解这三种药物与 EGFR 的潜在结合特征，有助于设计新的更有效的类似物。
