Combining structure-based and 3D QSAR pharmacophore models to discover diverse ligands against EGFR in oral cancer

Autor:	Purbali Chakraborty, Sajeli Begum Ahil, Trinath Jamma, Perumal Yogeeswari
Rok vydání:	2022
Předmět:	ErbB Receptors Pharmacology Lung Neoplasms Drug Resistance Neoplasm Mutation Drug Discovery Humans Quantitative Structure-Activity Relationship Molecular Medicine Mouth Neoplasms Ligands Protein Kinase Inhibitors
Zdroj:	Future Medicinal Chemistry. 14:463-478
ISSN:	1756-8927 1756-8919
Popis:	Background: Epidermal growth factor receptor-tyrosine kinase (EGFR-TK) is a well-known hallmark of oral and oropharyngeal cancers, as its overexpression leads to poor prognosis and malignancy. The activating EGFR mutations (particularly T790M and L858R double mutant) are a major challenge causing drug resistance, especially in the treatment of oral cancers. Methodology: This paper is an effort to exploit both structure-based and ligand-based pharmacophore modeling to discover EGFR-TK inhibitors, which show inhibition of proliferation of erlotinib-resistant FaDu and Cal27 oral cancer cells. Interestingly, the hit compound H2 also showed an effect on the downstream glucose and lactate metabolism pathways. Conclusion: The results indicate the potential of H2 to be developed as an EGFR-based metabolic inhibitor for oral cancer treatment.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f65cfaeee4086be67f76ccfe45e4ab0 https://doi.org/10.4155/fmc-2021-0205 Zobrazit plný text záznamu