Discovery of a series of novel phenylpiperazine derivatives as EGFR TK inhibitors

Scientific Reports
Juan SunHai-Liang Zhu

Abstract

Human epidermal growth factor receptor (EGFR) is an important drug target that plays a fundamental role in signal transduction pathways in oncology. We report herein the discovery of a novel class of phenylpiperazine derivatives with improved potency toward EGFR. The biological activity of compound 3p as inhibitor of EGFR was further investigated both in vitro and in vivo. Notably, compound 3p exhibited an IC50 in the nanomolar range in A549 cell cultures and induced a cessation of tumor growth with no toxicity, as determined by loss of body weight and death of treated mice. Compoutational docking studies also showed that compound 3p has interaction with EGFR key residues in the active site.

References

May 26, 1998·Environmental Health Perspectives·E Walum
Jul 18, 2002·Nature Reviews. Drug Discovery·Margaret A Somerville
Aug 28, 2002·The Journal of Biological Chemistry·Jennifer StamosCharles Eigenbrot
Dec 10, 2002·Science·G ManningS Sudarsanam
Jun 18, 2003·Accounts of Chemical Research·Alexander Levitzki
Jul 27, 2004·Antimicrobial Agents and Chemotherapy·Xin HeKevin A Reynolds
Sep 19, 2006·Bioorganic & Medicinal Chemistry Letters·Shenlin HuangLee M Greenberger
Jul 6, 2007·Bioorganic & Medicinal Chemistry Letters·Micheal D GaulChristian A Baumann
Sep 6, 2008·European Journal of Medicinal Chemistry·Venkateshappa ChandregowdaG Chandrasekara Reddy
Dec 17, 2009·Journal of Medicinal Chemistry·Fabio ZuccottoMauro Angiolini
Nov 23, 2011·European Journal of Medicinal Chemistry·Jee-Young LeeYangmee Kim
Nov 13, 2012·European Journal of Medicinal Chemistry·Samar MowafyKhaled A M Abouzid

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Methods Mentioned

BETA
flow cytometry
X
-ray
ELISA
Assay
X-ray

Software Mentioned

CDOCKER
flowjo
Discovery Studio
SPSS
DS
3D ultra
MMFF94

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