Farnesyltransferase and geranylgeranyltransferase I: structures, mechanism, inhibitors and molecular modeling

Mingyun Shen; Peichen Pan; Youyong Li; Dan Li; Huidong Yu; Tingjun Hou

doi:10.1016/j.drudis.2014.10.002

Farnesyltransferase and geranylgeranyltransferase I: structures, mechanism, inhibitors and molecular modeling

Drug Discov Today. 2015 Feb;20(2):267-76. doi: 10.1016/j.drudis.2014.10.002. Epub 2014 Oct 16.

Authors

Mingyun Shen¹, Peichen Pan¹, Youyong Li², Dan Li³, Huidong Yu⁴, Tingjun Hou⁵

Affiliations

¹ Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123, China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
² Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123, China.
³ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
⁴ Crystal Pharmatech, 707 Alexander Road Building 2, Suite 208, Princeton, NJ 08540, USA. Electronic address: huidongyu@yahoo.com.
⁵ Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 215123, China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: tingjunhou@zju.edu.cn.

PMID: 25450772
DOI: 10.1016/j.drudis.2014.10.002

Abstract

Farnesyltransferase (FTase) and geranylgeranyltransferase type I (GGTase-I) have crucial roles in the post-translational modifications of Ras proteins and, therefore, they are promising therapeutic targets for the treatment of various Ras-induced cancers and several other kinds of diseases. In this review, we provide an overview of the structures and biological functions of FTase and GGTase-I. Then, we summarize the typical inhibitors of FTase and GGTase-I, and highlight the drug candidates in clinical trials. In addition, we survey some recent advances in computer-aided drug design (CADD) and molecular modeling studies of FTase and GGTase-I.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Alkyl and Aryl Transferases* / antagonists & inhibitors
Alkyl and Aryl Transferases* / chemistry
Alkyl and Aryl Transferases* / metabolism
Animals
Farnesyltranstransferase* / antagonists & inhibitors
Farnesyltranstransferase* / chemistry
Farnesyltranstransferase* / metabolism
Humans
Models, Molecular
Protein Conformation

Substances

Alkyl and Aryl Transferases
geranylgeranyltransferase type-I
Farnesyltranstransferase