ArticleOncotarget2016
Conjugation to the sigma-2 ligand SV119 overcomes uptake blockade and converts dm-Erastin into a potent pancreatic cancer therapeutic.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 28 citations in OpenAlex.
- Differential Sensitivity to xCT-inhibition by ME1 expression.Molecular cancer therapeutics · 2026Article
- Trametinib Thwarts Activation of Survival Pathways Induced by Pro-ferroptotic Drug Conjugate ACXT-3102 Resulting in Enhanced Pancreatic Cancer Cell Death.Molecular cancer therapeutics · 2025Article
- Sigma‑2 Receptor/Transmembrane Protein 97 in Pain Modulation: Tracing Historical Roots and Current Research Directions.ACS pharmacology & translational science · 2025Review
- Recent Advances in the Development of Sigma Receptor (Radio)Ligands and Their Application in Tumors.ACS pharmacology & translational science · 2025Review
- Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress.Cell death & disease · 2024Article
- The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer.Scientific reports · 2024Article
- Harnessing ferroptosis for enhanced sarcoma treatment: mechanisms, progress and prospects.Experimental hematology & oncology · 2024Review
- Thiazole, Isatin and Phthalimide Derivatives TestedCurrent medicinal chemistry · 2024Review
- Relapsed Synovial Sarcoma: Treatment Options.Current treatment options in oncology · 2023Review
- Malic Enzyme 1 Absence in Synovial Sarcoma Shifts Antioxidant System Dependence and Increases Sensitivity to Ferroptosis Induction with ACXT-3102.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Overview of Ferroptosis and Synthetic Lethality Strategies.International journal of molecular sciences · 2021Review
- σMolecules (Basel, Switzerland) · 2021Review
- Sigma-2 Receptor-A Potential Target for Cancer/Alzheimer's Disease Treatment via Its Regulation of Cholesterol Homeostasis.Molecules (Basel, Switzerland) · 2020Review
- The Mechanism of Ferroptosis and Applications in Tumor Treatment.Frontiers in pharmacology · 2020Review
- TMEM97 and PGRMC1 do not mediate sigma-2 ligand-induced cell death.Cell death discovery · 2019Article
- The Relationship between Ferroptosis and Tumors: A Novel Landscape for Therapeutic Approach.Current gene therapy · 2019Review
- Multifunctional thiosemicarbazones and deconstructed analogues as a strategy to study the involvement of metal chelation, Sigma-2 (σEuropean journal of medicinal chemistry · 2018Article
- The Targeted SMAC Mimetic SW IV-134 is a strong enhancer of standard chemotherapy in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Cancer-selective drug delivery is an important concept in improving treatment while minimizing off-site toxicities, and sigma-2 receptors, which are overexpressed in solid tumors, represent attractive pharmacologic targets. Select sigma-2 ligands have been shown to be rapidly internalized selectively into cancer cells while retaining the capacity to deliver small molecules as drug cargoes. We utilized the sigma-2-based drug delivery concept to convert Erastin, a clinically underperforming drug, into a potent pancreatic cancer therapeutic. The Erastin derivative des-methyl Erastin (dm-Erastin) was chemically linked to sigma-2 ligand SV119 to create SW V-49. Conjugation increased the killing capacity of dm-Erastin by nearly 35-fold in vitro and reduced the size of established tumors and doubled the median survival in syngeneic and patient-derived xenograft models when compared to non-targeted dm-Erastin. Mechanistic analyses demonstrated that cell death was associated with robust reactive oxygen species production and could be efficiently antagonized with antioxidants. Mass spectrometry was employed to demonstrate selective uptake into pancreatic cancer cells. Thus, targeted delivery of dm-Erastin via conjugation to the sigma-2 ligand SV119 produced efficient tumor control and prolonged animal survival with minimal off-target toxicities, and SW V-49 represents a promising new therapeutic with the potential to advance the fight against 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.