ArticleJournal of medicinal chemistry2018
Design and Synthesis of Novel Reactive Oxygen Species Inducers for the Treatment of Pancreatic Ductal Adenocarcinoma.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review.Cell communication and signaling : CCS · 2019Pooled it
- QD394 induces ferroptosis and suppresses the proliferation of colorectal cancer via the SP1/JNK pathway.Apoptosis : an international journal on programmed cell death · 2026Article
- Design, synthesis, and antimicrobial evaluation of heteroaromatic or acyl-substituted benzenesulfonamide-linked aminoquinolinequinones.Folia microbiologica · 2026Article
- Melatonin-induced ferroptosis in pancreatic cancer cells by stimulating endoplasmic reticulum stress and inhibiting alanine-serine-cysteine transporter 2-driven glutamine metabolism.World journal of gastroenterology · 2025Article
- Targeted mitochondrial therapy for pancreatic cancer.Translational oncology · 2025Review
- Modification in Structures of Active Compounds in Anticancer Mitochondria-Targeted Therapy.International journal of molecular sciences · 2025Review
- Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches.Drug design, development and therapy · 2024Review
- Development of Prognostic Features of Hepatocellular Carcinoma Based on Metabolic Gene Classification and Immune and Oxidative Stress Characteristic Analysis.Oxidative medicine and cellular longevity · 2023Article
- 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
- Molecular regulatory mechanism of ferroptosis and its role in gastrointestinal oncology: Progress and updates.World journal of gastrointestinal oncology · 2022Review
- Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer.Molecules (Basel, Switzerland) · 2021Review
- Targeting Redox Metabolism in Pancreatic Cancer.International journal of molecular sciences · 2021Review
- A Novel Triphenylphosphonium Carrier to Target Mitochondria without Uncoupling Oxidative Phosphorylation.Journal of medicinal chemistry · 2021Article
- A Novel Redox Modulator Induces a GPX4-Mediated Cell Death That Is Dependent on Iron and Reactive Oxygen Species.Journal of medicinal chemistry · 2020Article
- Review
- DMAP-Catalyzed One-Pot Synthesis of Quinazoline-2,4-diones from 2-Aminobenzamides and Di-ACS omega · 2020Article
- Paradoxical Roles of Oxidative Stress Response in the Digestive System before and after Carcinogenesis.Cancers · 2019Review
- Synthesis and mechanistic studies of quinolin-chlorobenzothioate derivatives with proteasome inhibitory activity in pancreatic cancer cell lines.European journal of medicinal chemistry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Altering redox homeostasis provides distinctive therapeutic opportunities for the treatment of pancreatic cancer. Quinazolinediones (QDs) are novel redox modulators that we previously showed to induce potent growth inhibition in pancreatic ductal adenocarcinoma (PDAC) cell lines. Our lead optimization campaign yielded QD325 as the most potent redox modulator candidate inducing substantial reactive oxygen species (ROS) in PDAC cells. Nascent RNA sequencing following treatments with the QD compounds revealed induction of stress responses in nucleus, endoplasmic reticulum, and mitochondria of pancreatic cancer cells. Furthermore, the QD compounds induced Nrf2-mediated oxidative stress and unfolded protein responses as demonstrated by dose-dependent increases in RNA synthesis of representative genes such as NQO1, HMOX1, DDIT3, and HSPA5. At higher concentrations, the QDs blocked mitochondrial function by inhibiting mtDNA transcription and downregulating the mtDNA-encoded OXPHOS enzymes. Importantly, treatments with QD325 were well tolerated in vivo and significantly delayed tumor growth in mice. Our study supports the development of QD325 as a new therapeutic in the treatment of PDAC.
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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.