Cargando…
Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90
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 impor...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Society of Applied Pharmacology
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012869/ https://www.ncbi.nlm.nih.gov/pubmed/27582553 http://dx.doi.org/10.4062/biomolther.2016.168 |
_version_ | 1782452069526929408 |
---|---|
author | Jun, Kyu-Yeon Kwon, Youngjoo |
author_facet | Jun, Kyu-Yeon Kwon, Youngjoo |
author_sort | Jun, Kyu-Yeon |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5012869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Korean Society of Applied Pharmacology |
record_format | MEDLINE/PubMed |
spelling | pubmed-50128692016-09-14 Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90 Jun, Kyu-Yeon Kwon, Youngjoo Biomol Ther (Seoul) Review 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. The Korean Society of Applied Pharmacology 2016-09 2016-09-01 /pmc/articles/PMC5012869/ /pubmed/27582553 http://dx.doi.org/10.4062/biomolther.2016.168 Text en Copyright ©2016, The Korean Society of Applied Pharmacology http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Jun, Kyu-Yeon Kwon, Youngjoo Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90 |
title | Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90 |
title_full | Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90 |
title_fullStr | Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90 |
title_full_unstemmed | Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90 |
title_short | Proposal of Dual Inhibitor Targeting ATPase Domains of Topoisomerase II and Heat Shock Protein 90 |
title_sort | proposal of dual inhibitor targeting atpase domains of topoisomerase ii and heat shock protein 90 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012869/ https://www.ncbi.nlm.nih.gov/pubmed/27582553 http://dx.doi.org/10.4062/biomolther.2016.168 |
work_keys_str_mv | AT junkyuyeon proposalofdualinhibitortargetingatpasedomainsoftopoisomeraseiiandheatshockprotein90 AT kwonyoungjoo proposalofdualinhibitortargetingatpasedomainsoftopoisomeraseiiandheatshockprotein90 |