ArticleJournal of medicinal chemistry2020
A Novel Redox Modulator Induces a GPX4-Mediated Cell Death That Is Dependent on Iron and Reactive Oxygen Species.
Article in Journal of medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- QD394 induces ferroptosis and suppresses the proliferation of colorectal cancer via the SP1/JNK pathway.Apoptosis : an international journal on programmed cell death · 2026Article
- Protein Post-Translational Modifications in the Regulation of Ferroptosis: New Opportunities and Challenges for Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Quinazolinone derivatives as potential anti‑tumor agents: Structural features and molecular mechanisms in inducing cell death (Review).International journal of molecular medicine · 2025Review
- Research progress on the mechanism of tumor cell ferroptosis regulation by epigenetics.Epigenetics · 2025Review
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- Liver X Receptor Activation Alleviates Hepatic Ischemia-Reperfusion Injury in Diabetes by Inhibiting NF-κB-NLRP3 Activation.Immunity, inflammation and disease · 2025Article
- Recent Progress of Glutathione Peroxidase 4 Inhibitors in Cancer Therapy.Mini reviews in medicinal chemistry · 2025Review
- Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.Acta pharmaceutica Sinica. B · 2024Review
- The C-terminal selenenylsulfide of extracellular/non-reduced thioredoxin reductase endows this protein with selectivity to small-molecule electrophilic reagents under oxidative conditions.Frontiers in molecular biosciences · 2024Article
- Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases.Signal transduction and targeted therapy · 2023Review
- Ferroptosis and tumor immunotherapy: A promising combination therapy for tumors.Frontiers in oncology · 2023Review
- A novel machine learning-based programmed cell death-related clinical diagnostic and prognostic model associated with immune infiltration in endometrial cancer.Frontiers in oncology · 2023Article
- PROTACs in gastrointestinal cancers.Molecular therapy oncolytics · 2022Review
- Induction of Genes Implicated in Stress Response and Autophagy by a Novel Quinolin-8-yl-nicotinamide QN523 in Pancreatic Cancer.Journal of medicinal chemistry · 2022Article
- The RNA-binding protein SND1 promotes the degradation of GPX4 by destabilizing the HSPA5 mRNA and suppressing HSPA5 expression, promoting ferroptosis in osteoarthritis chondrocytes.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- The expression of mGland surgery · 2022Article
- Prognostication of Pancreatic Cancer Using The Cancer Genome Atlas Based Ferroptosis-Related Long Non-Coding RNAs.Frontiers in genetics · 2022Article
- Propofol induces the ferroptosis of colorectal cancer cells by downregulating STAT3 expression.Oncology letters · 2021Article
- Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91.Journal of medicinal chemistry · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Redox modulators have been developed as an attractive approach to treat cancer. Herein, we report the synthesis, identification, and biological evaluation of a quinazolinedione reactive oxygen species (ROS) inducer, QD394, with significant cytotoxicity in pancreatic cancer cells. QD394 shows a transcriptomic profile remarkably similar to napabucasin, a cancer stemness inhibitor. Both small molecules inhibit STAT3 phosphorylation, increase cellular ROS, and decrease the GSH/GSSG ratio. Moreover, QD394 causes an iron- and ROS-dependent, GPX4 mediated cell death, suggesting ferroptosis as a major mechanism. Importantly, QD394 decreases the expression of LRPPRC and PNPT1, two proteins involved in mitochondrial RNA catabolic processes and both negatively correlated with the overall survival of pancreatic cancer patients. Pharmacokinetics-guided lead optimization resulted in the derivative QD394-Me, which showed improved plasma stability and reduced toxicity in mice compared to QD394. Overall, QD394 and QD394-Me represent novel ROS-inducing drug-like compounds warranting further development for the treatment of pancreatic cancer.
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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.