TY - JOUR
T1 - Proposal of dual inhibitor targeting atpase domains of topoisomerase II and heat shock protein 90
AU - Jun, Kyu Yeon
AU - Kwon, Youngjoo
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (NRF-2013R1A1A2060408), the Korean Health Technology R&D Project funded by Ministry of Health & Welfare, Republic of Korea (HI14C2469), and by the grant of the Bio & Medical Technology Development Program (NRF- 2014M3A9A9073 908) of the National Research Foundation of Korea (NRF), funded by the Korean government (Ministry of Science, ICT & Future Planning).
Publisher Copyright:
© 2016 The Korean Society of Applied Pharmacology.
PY - 2016/9
Y1 - 2016/9
N2 - 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.
AB - 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.
KW - Design of dual inhibitor
KW - Heat shock protein 90
KW - Molecular docking study
KW - Topoisomerase II
UR - http://www.scopus.com/inward/record.url?scp=84988419951&partnerID=8YFLogxK
U2 - 10.4062/biomolther.2016.168
DO - 10.4062/biomolther.2016.168
M3 - Article
AN - SCOPUS:84988419951
SN - 1976-9148
VL - 24
SP - 453
EP - 468
JO - Biomolecules and Therapeutics
JF - Biomolecules and Therapeutics
IS - 5
ER -