Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening

Yanyu Ma; Yidan Song; Junyi Wang; Xiayu Shi; Zhen Yuan; Shuang Li; Honglin Li; Zhuo Chen; Shiliang Li

doi:10.4155/fmc-2023-0301

Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening

Yanyu Ma
, Yidan Song
, Junyi Wang
, Xiayu Shi
, Zhen Yuan
, Shuang Li
, Honglin Li
, Zhuo Chen^*
, Shiliang Li

^*Corresponding author for this work

School of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	665-677
Number of pages	13
Journal	Future Medicinal Chemistry
Volume	16
Issue number	7
DOIs	https://doi.org/10.4155/fmc-2023-0301
State	Published - 2024

Keywords

DJ-1
cancer treatment
covalent inhibitor
molecular docking
virtual screening

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4155/fmc-2023-0301

Cite this

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title = "Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening",

abstract = "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.",

keywords = "DJ-1, cancer treatment, covalent inhibitor, molecular docking, virtual screening",

author = "Yanyu Ma and Yidan Song and Junyi Wang and Xiayu Shi and Zhen Yuan and Shuang Li and Honglin Li and Zhuo Chen and Shiliang Li",

note = "Publisher Copyright: {\textcopyright} 2024 Expert Publishing Science Ltd trading as Taylor \& Francis.",

year = "2024",

doi = "10.4155/fmc-2023-0301",

language = "英语",

volume = "16",

pages = "665--677",

journal = "Future Medicinal Chemistry",

issn = "1756-8919",

publisher = "Taylor and Francis Ltd.",

number = "7",

}

TY - JOUR

T1 - Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening

AU - Ma, Yanyu

AU - Song, Yidan

AU - Wang, Junyi

AU - Shi, Xiayu

AU - Yuan, Zhen

AU - Li, Shuang

AU - Li, Honglin

AU - Chen, Zhuo

AU - Li, Shiliang

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - DJ-1

KW - cancer treatment

KW - covalent inhibitor

KW - molecular docking

KW - virtual screening

UR - https://www.scopus.com/pages/publications/85187775609

U2 - 10.4155/fmc-2023-0301

DO - 10.4155/fmc-2023-0301

M3 - 文章

C2 - 38390730

AN - SCOPUS:85187775609

SN - 1756-8919

VL - 16

SP - 665

EP - 677

JO - Future Medicinal Chemistry

JF - Future Medicinal Chemistry

IS - 7

ER -

Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening

Abstract

Keywords

UN SDGs

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