Discovery of novel inhibitors for human farnesyltransferase (hFTase) via structure-based virtual screening

Xiaojuan Yu; Xue Zhao; Lili Zhu; Chuanxin Zou; Xiaofeng Liu; Zhenjiang Zhao; Jin Huang; Honglin Li

doi:10.1039/C3MD00058C

Discovery of novel inhibitors for human farnesyltransferase (hFTase) via structure-based virtual screening

Xiaojuan Yu,^a Xue Zhao,^a Lili Zhu,^a Chuanxin Zou,^a Xiaofeng Liu,^a Zhenjiang Zhao,^a Jin Huang*^a and Honglin Li*^a

* Corresponding authors

^a State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China
E-mail: huangjin@ecust.edu.cn, hlli@ecust.edu.cn
Fax: +86-21-64250213
Tel: +86-21-64250213

Abstract

In this study, 22 novel hFTase inhibitors containing 18 scaffolds were identified with IC₅₀ values ranging from 0.0119 to 13.35 μM by structure-based virtual screening, and compounds 2, 7, 9, 10, 14 and 15 showed moderate antiproliferative activity against MCF-7 cells. In particular, compound 2 was the most promising lead compound with nanomolar activity against FTase and antiproliferative activity in the low micromolar range. Possible binding modes of the hit compounds were explored and their structure–activity relationships (SAR) were elucidated by molecular docking simulation. The hit compounds discovered in this work will provide novel scaffolds for further hit-to-lead optimization and lay the foundation for further development of therapeutic candidates for cancer treatments.

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Publication details

The article was received on 21 Feb 2013, accepted on 10 Apr 2013 and first published on 10 Apr 2013

Article type: Concise Article

DOI: 10.1039/C3MD00058C

Citation: Med. Chem. Commun., 2013,4, 962-971

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Discovery of novel inhibitors for human farnesyltransferase (hFTase) via structure-based virtual screening

X. Yu, X. Zhao, L. Zhu, C. Zou, X. Liu, Z. Zhao, J. Huang and H. Li, Med. Chem. Commun., 2013, 4, 962
DOI: 10.1039/C3MD00058C
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MedChemComm

Discovery of novel inhibitors for human farnesyltransferase (hFTase) via structure-based virtual screening

Abstract

Supplementary files

Publication details

Discovery of novel inhibitors for human farnesyltransferase (hFTase) via structure-based virtual screening

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