Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90.
10.4062/biomolther.2016.168
- Author:
Kyu Yeon JUN
1
;
Youngjoo KWON
Author Information
1. College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea. ykwon@ewha.ac.kr
- Publication Type:Review
- Keywords:
Topoisomerase II;
Heat shock protein 90;
Molecular docking study;
Design of dual inhibitor
- MeSH:
Adenosine Triphosphatases*;
Adenosine Triphosphate;
Binding Sites;
Cell Proliferation;
DNA Topoisomerases, Type II*;
Heat-Shock Proteins*;
Histidine;
Hot Temperature*;
Humans;
Phosphotransferases
- From:Biomolecules & Therapeutics
2016;24(5):453-468
- CountryRepublic of Korea
- Language:English
-
Abstract:
There is a conserved ATPase domain in topoisomerase II (topo II) and heat shock protein 90 (Hsp90) which belong to the GHKL (gyrase, Hsp90, histidine kinase, and MutL) family. The inhibitors that target each of topo II and Hsp90 are intensively studied as anti-cancer drugs since they play very important roles in cell proliferation and survival. Therefore the development of dual targeting anti-cancer drugs for topo II and Hsp90 is suggested to be a promising area. The topo II and Hsp90 inhibitors, known to bind to their ATP binding site, were searched. All the inhibitors investigated were docked to both topo II and Hsp90. Four candidate compounds as possible dual inhibitors were selected by analyzing the molecular docking study. The pharmacophore model of dual inhibitors for topo II and Hsp90 were generated and the design of novel dual inhibitor was proposed.
