ArticleNature communications2017
A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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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
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.
- Prognostic value of peptidyl-prolyl cis-trans isomerase 1 (PIN1) in human malignant tumors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Pooled it
- Exploring Non-Covalent Pin1-PROTACs Insights Into Degradation Efficiency in Multiple Myeloma Cell Line.Chemistry & biodiversity · 2026Article
- The Effect of Prolyl Isomerase Pin1 on the Development of Metabolic Dysfunction-Associated Steatohepatitis and a New Treatment Strategy.International journal of molecular sciences · 2026Review
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Systematic Optimization of Proteolysis-Targeting Chimeras for PIN1 Enables Selective Degradation and Antitumor Activity In Vivo.Pharmaceutics · 2026Article
- Prolyl-isomerase Pin1 drives platinum resistance by regulating Notch3 stability and function in ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Scaffold Hopping and Optimization of Thiazole Hybrids as Selective PIN1 Inhibitors: A Computational Study.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2026Article
- Pre-clinical evaluation of a potent and effective Pin1-degrading agent in pancreatic cancer.Molecular therapy. Oncology · 2025Article
- The Prolyl Isomerase PIN1 Affects Fibroblast Differentiation States and Cross-talk in Pancreatic Cancer.Cancer research · 2025Article
- Programmable immunoprobiotics orchestrate antitumor immune response with Pin1 inhibition for pancreatic cancer treatment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A tethering mechanism underlies Pin1-catalyzed prolineProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The PIN1-p38-CtIP signalling axis protects stalled replication forks from deleterious degradation.Nucleic acids research · 2025Article
- Identification and inhibition of PIN1-NRF2 protein-protein interactions through computational and biophysical approaches.Scientific reports · 2025Article
- PIN1 Prolyl Isomerase Promotes Initiation and Progression of Bladder Cancer through the SREBP2-Mediated Cholesterol Biosynthesis Pathway.Cancer discovery · 2025Article
- Discovery of Novel Pyrimidine Derivatives as Human Pin1 Covalent Inhibitors.ACS medicinal chemistry letters · 2025Article
- Common Signaling Pathways in Cancer and Alzheimer's Disease May Point to New Treatments.Current topics in medicinal chemistry · 2025Review
- Non-canonical Function of Prolyl Hydroxylase Domain 2 in Breast Cancer Cell Growth and Progression: Role of Peptidyl-prolyl Cis-trans Isomerase NIMA-interacting 1.Journal of cancer prevention · 2024Article
- Targeted degradation of Pin1 by protein-destabilizing compounds.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
29 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
24 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority of cancers and its activity strongly contributes to tumour initiation and progression. Inactivation of PIN1 function conversely curbs tumour growth and cancer stem cell expansion, restores chemosensitivity and blocks metastatic spread, thus providing the rationale for a therapeutic strategy based on PIN1 inhibition. Notwithstanding, potent PIN1 inhibitors are still missing from the arsenal of anti-cancer drugs. By a mechanism-based screening, we have identified a novel covalent PIN1 inhibitor, KPT-6566, able to selectively inhibit PIN1 and target it for degradation. We demonstrate that KPT-6566 covalently binds to the catalytic site of PIN1. This interaction results in the release of a quinone-mimicking drug that generates reactive oxygen species and DNA damage, inducing cell death specifically in cancer cells. Accordingly, KPT-6566 treatment impairs PIN1-dependent cancer phenotypes in vitro and growth of lung metastasis in vivo.
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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.