Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening
Background: DJ-1 is a ubiquitously expressed protein with multiple functions. Its overexpression has been associated with the occurrence of several cancers, positioning DJ-1 as a promising therapeutic target for cancer treatment. Methods: To find novel inhibitors of DJ-1, we employed a hybrid virtual screening strategy that combines structure-based and ligand-based virtual screening on a comprehensive compound library. Results: In silico study identified six hit compounds as potential DJ-1 inhibitors that were assessed in vitro at the cellular level. Compound 797780-71-3 exhibited antiproliferation activity in ACHN cells with an IC50 value of 12.18 μM and was able to inhibit the Wnt signaling pathway. This study discovers a novel covalent inhibitor for DJ-1 and paves the way for further optimization.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
|---|---|
| Enthalten in: |
Future medicinal chemistry - 16(2024), 7 vom: 20. März, Seite 665-677 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ma, Yanyu [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antineoplastic Agents |
|---|
| Anmerkungen: |
Date Completed 13.03.2024 Date Revised 29.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.4155/fmc-2023-0301 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368807207 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368807207 | ||
| 003 | DE-627 | ||
| 005 | 20240331001008.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.4155/fmc-2023-0301 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1357.xml |
| 035 | |a (DE-627)NLM368807207 | ||
| 035 | |a (NLM)38390730 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ma, Yanyu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening |
| 264 | 1 | |c 2024 | |
| 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 13.03.2024 | ||
| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Background: DJ-1 is a ubiquitously expressed protein with multiple functions. Its overexpression has been associated with the occurrence of several cancers, positioning DJ-1 as a promising therapeutic target for cancer treatment. Methods: To find novel inhibitors of DJ-1, we employed a hybrid virtual screening strategy that combines structure-based and ligand-based virtual screening on a comprehensive compound library. Results: In silico study identified six hit compounds as potential DJ-1 inhibitors that were assessed in vitro at the cellular level. Compound 797780-71-3 exhibited antiproliferation activity in ACHN cells with an IC50 value of 12.18 μM and was able to inhibit the Wnt signaling pathway. This study discovers a novel covalent inhibitor for DJ-1 and paves the way for further optimization | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DJ-1 | |
| 650 | 4 | |a cancer treatment | |
| 650 | 4 | |a covalent inhibitor | |
| 650 | 4 | |a molecular docking | |
| 650 | 4 | |a virtual screening | |
| 650 | 7 | |a Protein Deglycase DJ-1 |2 NLM | |
| 650 | 7 | |a EC 3.1.2.- |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 700 | 1 | |a Song, Yidan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Junyi |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xiayu |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Honglin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhuo |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shiliang |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Future medicinal chemistry |d 2009 |g 16(2024), 7 vom: 20. März, Seite 665-677 |w (DE-627)NLM194822109 |x 1756-8927 |7 nnns |
| 773 | 1 | 8 | |g volume:16 |g year:2024 |g number:7 |g day:20 |g month:03 |g pages:665-677 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.4155/fmc-2023-0301 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 16 |j 2024 |e 7 |b 20 |c 03 |h 665-677 | ||