ALL libraries (COBIB.SI union bibliographic/catalogue database)
-
In silico discovery and optimisation of a novel structural class of Hsp90 C-terminal domain inhibitors [Elektronski vir]Zajec, Živa, farmacevtka ...Hsp90 is a promising target for the development of novel agents for cancer treatment. The N-terminal Hsp90 inhibitors have several therapeutic limitations, the most important of which is the ... induction of heat shock response, which can be circumvented by targeting the allosteric binding site on the C-terminal domain (CTD) of Hsp90. In the absence of an Hsp90—CTD inhibitor co-crystal structure, the use of structure-based design approaches for the Hsp90 CTD is difficult and the structural diversity of Hsp90 CTD inhibitors is limited. In this study, we describe the discovery of a novel structural class of Hsp90 CTD inhibitors. A structure-based virtual screening was performed by docking a library of diverse compounds to the Hsp90β CTD binding site. Three selected virtual hits were tested in the MCF-7 breast cancer cell line, with compound TVS-23 showing antiproliferative activity with an IC50 value of 26.4 ± 1.1 µM. We report here the optimisation, synthesis and biological evaluation of TVS-23 analogues. Several analogues showed significantly enhanced antiproliferative activities in MCF-7 breast cancer and SK-N-MC Ewing sarcoma cell lines, with 7l being the most potent (IC50 = 1.4 ± 0.4 µM MCF-7; IC50 = 2.8 ± 0.4 µM SK-N-MC). The results of this study highlight the use of virtual screening to expand the structural diversity of Hsp90 CTD inhibitors and provide new starting points for further development.Source: Biomolecules [Elektronski vir]. - ISSN 2218-273X (Vol. 12, iss. 7, art 884, 2022, 23 str.)Type of material - e-article ; adult, seriousPublish date - 2022Language - englishCOBISS.SI-ID - 113870339
Author
Zajec, Živa, farmacevtka |
Dernovšek, Jaka |
Gobec, Martina, 1983- |
Tomašič, Tihomir
Topics
Rak (medicina) |
allosteric |
cancer |
heat shock |
Hsp90 |
inhibitor |
virtual screening |
alosterični |
toplotni šok |
Hsp90 |
inhibitorji |
virtualno rešetanje
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Author | Zajec, Živa, farmacevtka ... |
Title | In silico discovery and optimisation of a novel structural class of Hsp90 C-terminal domain inhibitors [Elektronski vir] |
Publication date | 2022-06-24 |
COBISS.SI-ID | 113870339 |
Publication version in repository | Publisher's version |
Publication licence | Creative Commons Attribution 4.0 International |
Embargo | Immediate publication for public |
Project(s) from which the publication was funded
Title | Acronym | Project ID | Funder |
---|---|---|---|
Razvoj novih zaviralcev Hsp90 s protitumornim delovanjem | J1-1717-2019 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin | P1-0208-2022 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
Files that belong to the publication
Link |
---|
![]() |
![]() |
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|---|
Zajec, Živa, farmacevtka | 53670 |
Dernovšek, Jaka | 54784 |
Gobec, Martina, 1983- | 32034 |
Tomašič, Tihomir | 28334 |
Source: Personal bibliographies
and: SICRIS
Select pickup location:
Material pickup by post
Delivery address:
Address is missing from the member's data.
The address retrieval service is currently unavailable, please try again.
By clicking the "OK" button, you will confirm the pickup location selected above and complete the reservation process.
By clicking the "OK" button, you will confirm the above pickup location and delivery address, and complete the reservation process.
By clicking the "OK" button, you will confirm the address selected above and complete the reservation process.
Notification
Automatic login and reservation service currently not available. You can reserve the material on the Biblos portal or try again here later.
Subject headings in COBISS General List of Subject Headings
Select pickup location
The material from the parent unit is free. If the material is delivered to the pickup location from another unit, the library may charge you for this service.
Pickup location | Material status | Reservation |
---|
Reservation in progress
Please wait a moment.
Reservation was successful.
Reservation failed.
Reservation...
Membership card:
Pickup location: