Anti‑breast cancer activity of selected 1,3,5‑triazines via modulation of EGFR‑TK

Molecular Medicine Reports
Weixin YanJianrong He

Abstract

The present study investigated the effect of certain 1,3,5‑triazine derivatives on epidermal growth factor receptor‑tyrosine kinase (EGFR‑TK). The results suggested that 1,3,5‑triazine derivatives exhibited optimal drug likeness via molinspiration and proved to be effective drug candidates as potential anticancer agents. The molecules were demonstrated to interact with key catalytic residues of EGFR, including Asn818, Lys721, Leu694, Val702 and Met742 as demonstrated in molecular docking experiments. Compound 1d was demonstrated to be the most potent analogue with an inhibitory constant of 0.44 nM, against EGFR‑TK in in‑vitro enzyme inhibition assay. Compound 1d was further evaluated for its effect on the cellular viability of three breast cancer cell lines, including highly metastatic MDAMB231, human epidermal growth factor receptor 2‑positive BT474 and estrogen receptorpositive MCF7 cells, using an MTT assay and apoptosis analysis. Western blot analysis was performed to examine the levels of β‑catenin in the control and treated cells. Based on the findings of the current study, the chemical 1,3,5‑triazine series are potential novel inhibitors of EGFR‑TK and β‑catenin signaling, and may be potent anti‑breast cancer agents.

References

Dec 19, 2008·European Journal of Human Genetics : EJHG·Tim RippergerBrigitte Schlegelberger
Dec 17, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Paula R PohlmannRay Mernaugh
Jul 10, 2010·Journal of the National Cancer Institute·Norman F BoydSalomon Minkin
Jul 14, 2010·Journal of Molecular Signaling·Kelly L MuellerJulie L Boerner
Oct 5, 2010·Annual Review of Medicine·C Kent Osborne, Rachel Schiff
Feb 26, 2011·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayDonald Maxwell Parkin
Jan 13, 2012·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Nov 13, 2012·European Journal of Medicinal Chemistry·Samar MowafyKhaled A M Abouzid
Jan 11, 2014·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Heae Surng ParkSo Yeon Park
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal

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Methods Mentioned

BETA
ELISA
fluorescence microscopy
protein assay

Software Mentioned

Docking Server
GraphPad
Image pro plus
AutoDock
Autogrid
Molinspiration
GraphPad Prism

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