Abstract
Abstract
Epidermal growth factor EGFR is an important target for non-small cell lung (NSCL) cancer, and inhibitors of AKT protein has been used in many cancer treatments including NSCL cancer. Therefore, screening small molecular inhibitors targeting both EGFR and AKT can help for cancer treatment. In this study, we screened Traditional Chinese Medicine on Immune-Oncology (TCMIO) database for potential natural product inhibitors that can target both EGFR and AKT using ligand-based pharmacophore model, molecular docking, and MD simulations methods. The human endogenous database HMDB was also screened. It was found that TCMIO89212, TCMIO90156 and TCMIO98874 from the TCMIO database had large binding free energies with EGFR and AKT. In the HMDB database, kinetin-7-N-glucoside was found to have ability to bind to EGFR and AKT. These results may provide valuable information for further experimental studies.
Publisher
Research Square Platform LLC
Reference57 articles.
1. Broekman, F. (2011). Tyrosine kinase inhibitors: multi-targeted or single-targeted? World journal of clinical oncology, 2(2), 80–93. Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK, Batra SK. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012 Jan;16(1):15–31. doi: 10.1517/14728222.2011.648617. Epub 2012 Jan 12. PMID: 22239438; PMCID: PMC3291787.
2. Harari PM. Epidermal growth factor receptor inhibition strategies in oncology. Endocr Relat Cancer. 2004 Dec;11(4):689–708. doi: 10.1677/erc.1.00600. PMID: 15613446.
3. Targeting the EGFR signaling pathway in cancer therapy;Seshacharyulu P;Expert Opin Ther Targets.,2012
4. Epidermal growth factor receptor targeting in cancer: a review of trends and strategies;Yewale C;Biomaterials.,2013
5. Jin Zhang,Jin-Sen Tang.Ergosta-7,22-diene-2β,3α,9α-triol (EGDT) from Ganoderma lucidum inhibits nasopharyngeal carcinoma cells by blocking EGFR signaling pathway[J];Chinese Herbal Medicines,2018