ArticleLeukemia2019
Inhibitors of the protein disulfide isomerase family for the treatment of multiple myeloma.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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
40 citing papers in PubMed, 56 citations in OpenAlex.
- Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer.JCI insight · 2019Trial
- Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha-Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer.Biomedicines · 2026Review
- A Phase I Clinical Study and In Vivo Findings with PT-112, a Novel Immunogenic Cell Death-Inducing Small Molecule, in Relapsed or Refractory Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Downregulation of PDIA4 inhibits proliferation and migration in human oral squamous cell carcinoma.Hereditas · 2025Article
- Bifunctional Cysteine-Engineered CAR‑T Cells Enable Thiol-Mediated Targeting to Overcome Antigen Escape in B Cell Lymphoma.ACS central science · 2025Article
- Protein disulfide isomerases regulate androgen receptor stability and promote prostate cancer cell growth and survival.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Single-cell analysis of the T-cell receptor repertoire in untreated myeloma patients suggests potential myelomareactive CD8Haematologica · 2025Article
- Pharmacological Modulation of the Unfolded Protein Response as a Therapeutic Approach in Cutaneous T-Cell Lymphoma.Biomolecules · 2025Article
- Current Novel Targeted Therapeutic Strategies in Multiple Myeloma.International journal of molecular sciences · 2024Review
- Activity-Based Protein Profiling Identifies Protein Disulfide-Isomerases as Target Proteins of the Volatile Salinilactones.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release.Journal of virology · 2024Article
- Functional characterization of the dimeric form of PDGF-derived fusion peptide fabricated based on theoretical arguments.Scientific reports · 2024Article
- Pan-Inhibition of Protein Disulfide Isomerase Caused Cell Death through Disrupting Cellular Proteostasis in Pancreatic Ductal Adenocarcinoma Cells.International journal of molecular sciences · 2023Article
- A chemical probe unravels the reactive proteome of health-associated catechols.Chemical science · 2023Article
- Thiol-Mediated Uptake of a Cysteine-Containing Nanobody for Anticancer Drug Delivery.ACS central science · 2023Article
- Deep Vein Thrombosis Is Facilitated by Endothelial-Derived Extracellular Vesicles via the PDI-GRP94-GPIIb/IIIa Pathway in Mice.Journal of clinical medicine · 2023Article
- Article
- The deubiquitinase OTUD1 regulates immunoglobulin production and proteasome inhibitor sensitivity in multiple myeloma.Nature communications · 2022Article
- Review
- Functions and mechanisms of protein disulfide isomerase family in cancer emergence.Cell & bioscience · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Multiple Myeloma (MM) is highly sensitive to disruptions in cellular protein homeostasis. Proteasome inhibitors (PIs) are initially effective in the treatment of MM, although cures are not achievable and the emergence of resistance limits the durability of responses. New therapies are needed for refractory patients, and those that combat resistance to standard of care agents would be particularly valuable. Screening of multiple chemical libraries for PI re-sensitizing compounds identified E61 as a potent enhancer of multiple PIs and MM specific activity. Using a tandem approach of click chemistry and peptide mass fingerprinting, we identified multiple protein disulfide isomerase (PDI) family members as the primary molecular targets of E61. PDIs mediate oxidative protein folding, and E61 treatment induced robust ER and oxidative stress responses as well as the accumulation of ubiquitinylated proteins. A chemical optimization program led to a new structural class of indene (exemplified by lead E64FC26), which are highly potent pan-style inhibitors of PDIs. In mice with MM, E64FC26 improved survival and enhanced the activity of bortezomib without any adverse effects. This work demonstrates the potential of E64FC26 as an early drug candidate and the strategy of targeting multiple PDI isoforms for the treatment of refractory MM and beyond.
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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.