ArticleCell reports2022
Characterization of a small molecule inhibitor of disulfide reductases that induces oxidative stress and lethality in lung cancer cells.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Glutathione reductase deficiency potentiates the immunogenicity of ferroptosis and cuproptosis via amplified reactive oxygen species accumulation and cGAS-STING pathway activation.Journal of hematology & oncology · 2026Article
- Recent advances in engineered nanozymes for precision lung cancer therapy.Materials today. Bio · 2026Review
- Vaccinia-related kinase 2 inhibition elicits vulnerability of glutathione metabolism in pancreatic cancer.Cell death & disease · 2026Article
- Tumor-intrinsic metabolic pathways essential for tumorigenesis and resistance to anti-PD1 in oncogenic Kras-driven lung adenocarcinoma.Cancer & metabolism · 2026Article
- Amodiaquine Enhances Anti-Melanoma Efficacy of Attenuated Salmonella via Targeting Glutathione Reductase in Neutrophils.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The novel thioredoxin reductase inhibitor butaselen suppresses lung cancer by inducing oxidative stress.Redox report : communications in free radical research · 2025Article
- PK11007 Covalently Inhibits Thioredoxin Reductase 1 to Induce Oxidative Stress and Autophagy Impairment in NSCLC Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Computer-Aided Discovery of Natural Compounds Targeting the ADAR2 dsRBD2-RNA Interface and Computational Modeling of Full-Length ADAR2 Protein Structure.International journal of molecular sciences · 2025Article
- Identification of an Amino Acid Metabolism Reprogramming Signature for Predicting Prognosis, Immunotherapy Efficacy, and Drug Candidates in Colon Cancer.Applied biochemistry and biotechnology · 2025Article
- The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.Journal of medicinal chemistry · 2024Review
- The Cancer Antioxidant Regulation System in Therapeutic Resistance.Antioxidants (Basel, Switzerland) · 2024Review
- Enzymatic Redox Properties and Cytotoxicity of Irreversible Nitroaromatic Thioredoxin Reductase Inhibitors in Mammalian Cells.International journal of molecular sciences · 2023Article
- Article
- A Shift in Thinking: Cellular Thermal Shift Assay-Enabled Drug Discovery.ACS medicinal chemistry letters · 2023Review
- Combined thioredoxin reductase and glutaminase inhibition exerts synergistic anti-tumor activity in MYC-high high-grade serous ovarian carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- PICKLES v3: the updated database of pooled in vitro CRISPR knockout library essentiality screens.Nucleic acids research · 2023Article
- S-Denitrosylation: A Crosstalk between Glutathione and Redoxin Systems.Antioxidants (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
26 authors at 8 institutions in 3 countries.
Funding
Abstract
Phenotype-based screening can identify small molecules that elicit a desired cellular response, but additional approaches are required to characterize their targets and mechanisms of action. Here, we show that a compound termed LCS3, which selectively impairs the growth of human lung adenocarcinoma (LUAD) cells, induces oxidative stress. To identify the target that mediates this effect, we use thermal proteome profiling (TPP) and uncover the disulfide reductases GSR and TXNRD1 as targets. We confirm through enzymatic assays that LCS3 inhibits disulfide reductase activity through a reversible, uncompetitive mechanism. Further, we demonstrate that LCS3-sensitive LUAD cells are sensitive to the synergistic inhibition of glutathione and thioredoxin pathways. Lastly, a genome-wide CRISPR knockout screen identifies NQO1 loss as a mechanism of LCS3 resistance. This work highlights the ability of TPP to uncover targets of small molecules identified by high-throughput screens and demonstrates the potential therapeutic utility of inhibiting disulfide reductases in LUAD.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.