Studies on the Dual Activity of EGFR and HER-2 Inhibitors Using Structure-Based Drug Design Techniques

International Journal of Molecular Sciences

Michellde Oliveira Almeida¹  KathiaMaria Honorio²  Heberth de Paula²  RafaelaMolina de Angelo² 

[1] Center for Natural and Human Sciences (CCNH), Federal University of ABC (UFABC), Santo André 09210-580, Brazil;School of Arts, Sciences and Humanities (EACH), University of São Paulo (USP), São Paulo 03828-000, Brazil;

关键词: cancer;    HER-2;    EGFR;    drug design;    docking;    CoMFA;    CoMSIA;    dual inhibitor;   

DOI  :  10.3390/ijms19123728

来源: DOAJ

【 摘 要 】

HER-2 and EGFR are biological targets related to the development of cancer and the discovery and/or development of a dual inhibitor could be a good strategy to design an effective drug candidate. In this study, analyses of the chemical properties of a group of substances having affinity for both HER-2 and EGFR were carried out with the aim of understanding the main factors involved in the interaction between these inhibitors and the biological targets. Comparative analysis of molecular interaction fields (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques were applied on 63 compounds. From CoMFA analyses, we found for both HER-2 (r² calibration = 0.98 and q²_cv = 0.83) and EGFR (r² calibration = 0.98 and q²_cv = 0.73) good predictive models. Good models for CoMSIA technique have also been found for HER-2 (r² calibration = 0.92 and q²_cv = 0.74) and EGFR (r² calibration = 0.97 and q²_cv = 0.72). The constructed models could indicate some important characteristics for the inhibition of the biological targets. New compounds were proposed as candidates to inhibit both proteins. Therefore, this study may guide future projects for the development of new drug candidates for the treatment of breast cancer.

【 授权许可】

Unknown