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New diarylamine KV10.1 inhibitors and their anticancer potential [Elektronski vir]Gubič, Špela ...Expression of the voltage-gated potassium channel KV10.1 (Eag1) has been detected in over 70% of human cancers, making the channel a promising new target for new anticancer drug discovery. A new ... structural class of KV10.1 inhibitors was prepared by structural optimisation and exploration of the structure–activity relationship of the previously published hit compound ZVS-08 (1) and its optimised analogue 2. The potency and selectivity of the new inhibitors between KV10.1 and hERG were investigated using whole-cell patch-clamp experiments. We obtained two new optimised KV10.1 inhibitors, 17a and 18b, with improved nanomolar IC50 values of 568 nM and 214 nM, respectively. Compound 17a exhibited better ratio between IC50 values for hEAG1 and hERG than previously published diarylamine inhibitors. Compounds 17a and 18b moderately inhibited the growth of the KV10.1-expressing cell line MCF-7 in two independent assays. In addition, 17a and 18b also inhibited the growth of hERG-expressing Panc-1 cells with higher potency compared with MCF-7 cells. The main obstacle for newly developed diarylamine KV10.1 inhibitors remains the selectivity toward the hERG channel, which needs to be addressed with targeted drug design strategies in the future.Source: Pharmaceutics [Elektronski vir]. - ISSN 1999-4923 (Vol. 14, iss. 9, art. 1963, 2022, 27 str.)Type of material - e-article ; adult, seriousPublish date - 2022Language - englishCOBISS.SI-ID - 121841667
Author
Gubič, Špela |
Toplak, Žan |
Shi, Xiaoyi |
Dernovšek, Jaka |
Hendrickx, Louise Antonia |
Lopes Pinheiro-Junior, Ernesto |
Peigneur, Steve |
Tytgat, Jan |
Pardo A., Luis |
Peterlin-Mašič, Lucija |
Tomašič, Tihomir
Topics
Ionski kanalčki |
KV10.1 |
ionski kanali |
hERG |
SAR |
antiproliferativno delovanje |
KV10.1 |
ion channels |
hERG |
SAR |
antiproliferative activity
Author | Gubič, Špela ... |
Title | New diarylamine KV10.1 inhibitors and their anticancer potential [Elektronski vir] |
Publication date | 2022-09-17 |
COBISS.SI-ID | 121841667 |
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 |
---|---|---|---|
Odkrivanje in mehanizem delovanja novih spojin vodnic hEag1 kalijevih kanalov s protirakavim delovanjem | N1-0098-2019 |
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 |
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https://www.mdpi.com/1999-4923/14/9/1963 |
https://repozitorij.uni-lj.si/IzpisGradiva.php?id=140829 |
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Gubič, Špela | 53671 |
Toplak, Žan | 52375 |
Shi, Xiaoyi | |
Dernovšek, Jaka | 54784 |
Hendrickx, Louise Antonia | |
Lopes Pinheiro-Junior, Ernesto | |
Peigneur, Steve | |
Tytgat, Jan | |
Pardo A., Luis | |
Peterlin-Mašič, Lucija | 19317 |
Tomašič, Tihomir | 28334 |
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