Structure based design of heat shock protein 90 inhibitors acting as anticancer agents

Title
Structure based design of heat shock protein 90 inhibitors acting as anticancer agents
Authors
무니크말레디또라트서선희홍태훈조용서한지숙배애님
Keywords
HSP90; anticancer; 항암제; SBDD; Virtual screening; Anticancer agents
Issue Date
2011-03
Publisher
Bioorganic & medicinal chemistry
Citation
VOL 19, NO 5, 1714-1720
Abstract
Structure based drug design (SBDD) was used to discover heat shock protein 90 (HSP90) inhibitors useful in the treatment of cancer. By using the crystal structure of HSP90–ligand complex (1uyi), a docking model was prepared and was validated by external dataset containing known HSP90 inhibitors. This validated model was then used to virtually screen commercial databases, selected hits of which were bought and sent for real biological evaluation. Further as an alternative method, pharmacophores were generated using crystal structure conformations of ligands in HSP90 complexes (1uyi and 2bz5) and where used for virtual screening. Both cases yielded several hits containing novel scaffolds, particularly compound KHSP8 showed an IC50 value of 0.902 lM in case of colon cancer (HT29), which is comparable to doxorubicin (0.828 μM). These compounds were being now used as leads for constructing small molecular libraries to get compounds with favourable pharmacokinetics and drug like properties.
URI
http://pubs.kist.re.kr/handle/201004/39912
ISSN
0968-0896
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE