ArticleMolecular cancer therapeutics2016
Acridine Derivatives as Inhibitors of the IRE1α-XBP1 Pathway Are Cytotoxic to Human Multiple Myeloma.
Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Regulatory Mechanisms of XBP1 in Tumorigenesis and Cancer Progression: Challenges and Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- SHP2 improves ovarian morphology and steroidogenic function in a rat PCOS model by modulating IRE1α/XBP1/NLRP3-mediated granulosa cell pyroptosis.Scientific reports · 2026Article
- WFS1 Gene Mutation (c.2389G > A) Induces Immune Disorders by Promoting DC Maturation through Inhibition of TMEM176A.Inflammation · 2025Article
- An Overview of Acridine Analogs: Pharmacological Significance and Recent Developments.Current medicinal chemistry · 2025Review
- Endoplasmic reticulum stress in lung cancer.Frontiers in oncology · 2025Review
- IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis.Nature communications · 2024Article
- Article
- Acridine as an Anti-Tumour Agent: A Critical Review.Molecules (Basel, Switzerland) · 2022Review
- Review
- Proteotoxic Stress as an Exploitable Vulnerability in Cells with Hyperactive AKT.International journal of molecular sciences · 2021Article
- The topology of data: opportunities for cancer research.Bioinformatics (Oxford, England) · 2021Article
- Triazoloacridone C-1305 impairs XBP1 splicing by acting as a potential IRE1α endoribonuclease inhibitor.Cellular & molecular biology letters · 2021Article
- The Structure, Activation and Signaling of IRE1 and Its Role in Determining Cell Fate.Biomedicines · 2021Review
- Development of Tumor-Targeting IRE-1 Inhibitors for B-cell Cancer Therapy.Molecular cancer therapeutics · 2020Article
- Fumarate hydratase-deficient renal cell carcinoma cells respond to asparagine by activation of the unfolded protein response and stimulation of the hexosamine biosynthetic pathway.Cancer & metabolism · 2020Article
- Proteostasis In The Endoplasmic Reticulum: Road to Cure.Cancers · 2019Review
- The Unfolded Protein Response in Breast Cancer.Cancers · 2018Review
- Inhibition of IRE1 results in decreased scar formation.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2017Article
- Novel Methylselenoesters as Antiproliferative Agents.Molecules (Basel, Switzerland) · 2017Article
- Targeting the unfolded protein response in cancer.Pharmacological research · 2017Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Using a luciferase reporter-based high-throughput chemical library screen and topological data analysis, we identified N-acridine-9-yl-N',N'-dimethylpropane-1,3-diamine (DAPA) as an inhibitor of the inositol requiring kinase 1α (IRE1α)-X-box binding protein-1 (XBP1) pathway of the unfolded protein response. We designed a collection of analogues based on the structure of DAPA to explore structure-activity relationships and identified N(9)-(3-(dimethylamino)propyl)-N(3),N(3),N(6),N(6)-tetramethylacridine-3,6,9-triamine (3,6-DMAD), with 3,6-dimethylamino substitution on the chromophore, as a potent inhibitor. 3,6-DMAD inhibited both IRE1α oligomerization and in vitro endoribonuclease (RNase) activity, whereas the other analogues only blocked IRE1α oligomerization. Consistent with the inhibition of IRE1α-mediated XBP1 splicing, which is critical for multiple myeloma cell survival, these analogues were cytotoxic to multiple myeloma cell lines. Furthermore, 3,6-DMAD inhibited XBP1 splicing in vivo and the growth of multiple myeloma tumor xenografts. Our study not only confirmed the utilization of topological data analysis in drug discovery but also identified a class of compounds with a unique mechanism of action as potent IRE1α-XBP1 inhibitors in the treatment of multiple myeloma. Mol Cancer Ther; 15(9); 2055-65. ©2016 AACR.
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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.