Computational evaluation and in vitro validation of new Epidermal Growth Factor Receptor inhibitors.

Computational evaluation and in vitro validation of new Epidermal Growth Factor Receptor inhibitors. Curr Top Med Chem. 2020 Jun 03;: Authors: Gómez-Ganau S, Castillo J, Cervantes A, de Julián Ortiz JV, Gozalbes R Abstract The epidermal growth factor receptor (EGFR) is a transmembrane protein that acts as a receptor of extracellular protein ligands of the epidermal growth factor (EGF/ErbB) family. It has been shown that EGFR is overexpressed by many tumours and correlates with poor prognosis. Therefore, EGFR can be considered as a very interesting therapeutic target for the treatment of a large variety of cancers such as lung, ovarian, endometrial, gastric, bladder and breast cancers, cervical adenocarcinoma, malignant melanoma and glioblastoma. We have followed a structure-based virtual screening (SBVS) procedure with a library composed by several commercial collections of chemicals (615,462 compounds in total) and the 3D structure of EGFR obtained from the Protein Data Bank (PDB code: 1M17). The docking results from this campaign were then ranked according to the theoretical binding affinity of these molecules to EGFR, and compared with the binding affinity of erlotinib, a well-known EGFR inhibitor. A total of 23 top-rated commercial compounds displaying potential binding affinities similar or even better than erlotinib were selected for experimental evaluation. In vitro assays in different cell lines were performed. A preliminar...
Source: Current Topics in Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Top Med Chem Source Type: research