Thimerosal, a competitive thioredoxin reductase 1 (TrxR1) inhibitor discovered via high-throughput screening
Copyright © 2023 Elsevier Inc. All rights reserved..
Thioredoxin reductase 1 (TrxR1) is considered as an important anti-cancer drug target, inhibition of which can induce reactive oxygen species (ROS)-mediated apoptosis of human cancer cells. Here, we developed and optimized a high-throughput screening (HTS) assay based on enzyme kinetics for the discovery of TrxR1 inhibitors. By utilizing this assay, we performed a HTS for 2500 compounds from an in-house library against TrxR1. We found that a vaccine preservative, thimerosal, strongly inhibited TrxR1 in a competitive and reversible manner with an IC50 of 24.08 ± 0.86 nM. In addition, we determined that thiomersal has an inhibitory effect on the proliferation of A549 lung cancer cell line, with a GI50 of 6.81 ± 0.09 μM, slightly more potent than auranofin (GI50 = 11.85 ± 0.56 μM). Furthermore, we showed by flow cytometer that thimerosal effectively increased the content of ROS in A549 cells. Therefore, our work provided a high-throughput screening assay to quickly and effectively discover TrxR1 inhibitors, identifying thiomersal as a novel TrxR1 inhibitor and chemical probe.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:650 |
---|---|
Enthalten in: |
Biochemical and biophysical research communications - 650(2023) vom: 02. Apr., Seite 117-122 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Ni, Yicheng [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 28.02.2023 Date Revised 21.03.2023 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.bbrc.2023.02.014 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM352901209 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM352901209 | ||
003 | DE-627 | ||
005 | 20231226054758.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.bbrc.2023.02.014 |2 doi | |
028 | 5 | 2 | |a pubmed24n1176.xml |
035 | |a (DE-627)NLM352901209 | ||
035 | |a (NLM)36780763 | ||
035 | |a (PII)S0006-291X(23)00174-2 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Ni, Yicheng |e verfasserin |4 aut | |
245 | 1 | 0 | |a Thimerosal, a competitive thioredoxin reductase 1 (TrxR1) inhibitor discovered via high-throughput screening |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 28.02.2023 | ||
500 | |a Date Revised 21.03.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
520 | |a Thioredoxin reductase 1 (TrxR1) is considered as an important anti-cancer drug target, inhibition of which can induce reactive oxygen species (ROS)-mediated apoptosis of human cancer cells. Here, we developed and optimized a high-throughput screening (HTS) assay based on enzyme kinetics for the discovery of TrxR1 inhibitors. By utilizing this assay, we performed a HTS for 2500 compounds from an in-house library against TrxR1. We found that a vaccine preservative, thimerosal, strongly inhibited TrxR1 in a competitive and reversible manner with an IC50 of 24.08 ± 0.86 nM. In addition, we determined that thiomersal has an inhibitory effect on the proliferation of A549 lung cancer cell line, with a GI50 of 6.81 ± 0.09 μM, slightly more potent than auranofin (GI50 = 11.85 ± 0.56 μM). Furthermore, we showed by flow cytometer that thimerosal effectively increased the content of ROS in A549 cells. Therefore, our work provided a high-throughput screening assay to quickly and effectively discover TrxR1 inhibitors, identifying thiomersal as a novel TrxR1 inhibitor and chemical probe | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Chemical probe | |
650 | 4 | |a High-throughput screening | |
650 | 4 | |a Thimerosal | |
650 | 4 | |a Thioredoxin reductase 1 inhibitor | |
650 | 7 | |a Thioredoxin Reductase 1 |2 NLM | |
650 | 7 | |a EC 1.8.1.9 |2 NLM | |
650 | 7 | |a Thimerosal |2 NLM | |
650 | 7 | |a 2225PI3MOV |2 NLM | |
650 | 7 | |a Reactive Oxygen Species |2 NLM | |
650 | 7 | |a Thioredoxin-Disulfide Reductase |2 NLM | |
650 | 7 | |a EC 1.8.1.9 |2 NLM | |
700 | 1 | |a Luo, Zhongyuan |e verfasserin |4 aut | |
700 | 1 | |a Lv, Yixin |e verfasserin |4 aut | |
700 | 1 | |a Ma, Shuyuan |e verfasserin |4 aut | |
700 | 1 | |a Luo, Cheng |e verfasserin |4 aut | |
700 | 1 | |a Du, Daohai |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Biochemical and biophysical research communications |d 1960 |g 650(2023) vom: 02. Apr., Seite 117-122 |w (DE-627)NLM000000035 |x 1090-2104 |7 nnns |
773 | 1 | 8 | |g volume:650 |g year:2023 |g day:02 |g month:04 |g pages:117-122 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bbrc.2023.02.014 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 650 |j 2023 |b 02 |c 04 |h 117-122 |