ArticleProceedings of the National Academy of Sciences of the United States of America2012
Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 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
129 citing papers in PubMed.
- Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer.JCI insight · 2019Trial
- Molecular mechanisms of protein disulfide isomerase antagonism by punicalagin.Biochemical and biophysical research communications · 2026Article
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- Article
- Enzyme-Inspired Design of Redox-Active Molecules for Promotion of Oxidative Protein Folding.Chembiochem : a European journal of chemical biology · 2026Review
- Genetically Encoding Propiolamide Warhead for the Construction of Phage Displayed Cyclic Peptide Library.Chembiochem : a European journal of chemical biology · 2026Article
- Luminespib and AZ5104 are effective antithrombotic drugs via targeting the platelet Ero1α-PDI pathway.Science advances · 2026Article
- PDIA1 promotes androgen receptor activation and prostate cancer cell survival through enhancing HMMR stability.FEBS letters · 2026Article
- Molecular insights into protein disulfide isomerase antagonism by punicalagin.bioRxiv : the preprint server for biology · 2026Article
- Targeting the Endoplasmic Reticulum Oxidoreductin-1 Alpha-Protein Disulfide Isomerase Redox Interface as a Therapeutic Strategy in Cancer.Biomedicines · 2026Review
- Assays of Thiol Isomerase Activity.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Tannic acid inhibits TNF-α signaling by targeting the protein disulfide isomerase and alleviates symptoms in an imiquimod-induced psoriasis mouse model.Cell communication and signaling : CCS · 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
- The Role of Endoplasmic Reticulum Stress and Unfolded Protein Response in Gynecological Cancers: A Narrative Review.Cureus · 2025Review
- Thiol Isomerases: Enzymatic Mechanisms, Models of Oxidation, and Antagonism by Galloylated Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Optimizing PDIA1 Inhibition as a Strategy to Inhibit NLRP3 Inflammasome Activation and Activity.ACS chemical biology · 2025Article
- Prospects for ferroptosis therapies in cancer.Nature cancer · 2025Review
- Extracellular PDI in thrombosis and vascular injury.Thrombosis journal · 2025Review
- Development of Zafirlukast Analogues for Improved Antithrombotic Activity Through Thiol Isomerase Inhibition.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Potential drug targets for ovarian cancer identified through Mendelian randomization and colocalization analysis.Journal of ovarian research · 2025Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein disulfide isomerase (PDI), an endoplasmic reticulum chaperone protein, catalyzes disulfide bond breakage, formation, and rearrangement. The effect of PDI inhibition on ovarian cancer progression is not yet clear, and there is a need for potent, selective, and safe small-molecule inhibitors of PDI. Here, we report a class of propynoic acid carbamoyl methyl amides (PACMAs) that are active against a panel of human ovarian cancer cell lines. Using fluorescent derivatives, 2D gel electrophoresis, and MS, we established that PACMA 31, one of the most active analogs, acts as an irreversible small-molecule inhibitor of PDI, forming a covalent bond with the active site cysteines of PDI. We also showed that PDI activity is essential for the survival and proliferation of human ovarian cancer cells. In vivo, PACMA 31 showed tumor targeting ability and significantly suppressed ovarian tumor growth without causing toxicity to normal tissues. These irreversible small-molecule PDI inhibitors represent an important approach for the development of targeted anticancer agents for ovarian cancer therapy, and they can also serve as useful probes for investigating the biology of PDI-implicated pathways.
Indexed as
Identifiers
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.