Biomol Ther.  2016 Sep;24(5):453-468. 10.4062/biomolther.2016.168.

Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90

• Jun KY
• Kwon Y

• KMID: 2351668
• DOI: http://doi.org/10.4062/biomolther.2016.168

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.

Keyword

Topoisomerase II; Heat shock protein 90; Molecular docking study; Design of dual inhibitor

MeSH Terms

Adenosine Triphosphatases*
Adenosine Triphosphate
Binding Sites
Cell Proliferation
DNA Topoisomerases, Type II*
Heat-Shock Proteins*
Histidine
Hot Temperature*
Humans
Phosphotransferases
Adenosine Triphosphatases
Adenosine Triphosphate
DNA Topoisomerases, Type II
Heat-Shock Proteins
Histidine
Phosphotransferases