Identification of Dual-Target Inhibitors for Epidermal Growth Factor Receptor and AKT: Virtual Screening Based on Structure and Molecular Dynamics Study.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Antineoplastic Agents*/pharmacology ; Carcinoma, Non-Small-Cell Lung*/drug therapy ; Lung Neoplasms*/drug therapy; Humans ; Molecular Dynamics Simulation ; Molecular Docking Simulation ; Proto-Oncogene Proteins c-akt/metabolism ; Protein Kinase Inhibitors/chemistry ; ErbB Receptors/metabolism

Epidermal growth factor EGFR is an important target for non-small cell lung (NSCL) cancer, and inhibitors of the AKT protein have been used in many cancer treatments, including those for NSCL cancer. Therefore, searching small molecular inhibitors which can target both EGFR and AKT may help cancer treatment. In this study, we applied a ligand-based pharmacophore model, molecular docking, and MD simulation methods to search for potential inhibitors of EGFR and then studied dual-target inhibitors of EGFR and AKT by screening the immune-oncology Chinese medicine (TCMIO) database and the human endogenous database (HMDB). It was found that TCMIO89212, TCMIO90156, and TCMIO98874 had large binding free energies with EGFR and AKT, and HMDB0012243 also has the ability to bind to EGFR and AKT. These results may provide valuable information for further experimental study.

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ZR2020QB104 Wencai Lu

Keywords: AKT; EGFR; HMDB; TCMIO; small molecule inhibitors

0 (Antineoplastic Agents)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
0 (Protein Kinase Inhibitors)
EC 2.7.10.1 (ErbB Receptors)

Date Created: 20231125 Date Completed: 20231127 Latest Revision: 20231127

20240829

PMC10673407

10.3390/molecules28227607

38005329