ArticleCancer research2016
Novel Anticancer Agents Based on Targeting the Trimer Interface of the PRL Phosphatase.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 46 citations in OpenAlex.
- Discovery of inhibitors of the cancer-promoting phosphatase PRL-3 and their evaluation in intestinal organoids.Bioorganic & medicinal chemistry · 2025Article
- Protein Tyrosine Phosphatase 4A1 (PTP4A1) Regulates Early Events in Colorectal Cancer Intraperitoneal Dissemination in the Aged Male Host.Aging and cancer · 2025Article
- Protein tyrosine phosphatase receptor type kappa (PTPRK) revisited: evolving insights into structure, function, and pathology.Journal of translational medicine · 2025Review
- The PRL2 phosphatase up-regulates miR-21 through activation of the JAK2/STAT3 pathway to down-regulate the PTEN tumor suppressor.The Biochemical journal · 2025Article
- Targeting PRL phosphatases in hematological malignancies.Expert opinion on therapeutic targets · 2024Review
- PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation.Molecular cancer research : MCR · 2024Article
- Inhibition of PRL2 Upregulates PTEN and Attenuates Tumor Growth in Tp53-deficient Sarcoma and Lymphoma Mouse Models.Cancer research communications · 2024Article
- Article
- Phosphatase-independent role of phosphatase of regenerating liver in cancer progression.Cancer science · 2023Review
- The role of oligomerization in the optimization of cyclohexadienyl dehydratase conformational dynamics and catalytic activity.Protein science : a publication of the Protein Society · 2022Article
- CharacterizingJournal of oncology · 2022Article
- A New Paradigm for KIM-PTP Drug Discovery: Identification of Allosteric Sites with Potential for Selective Inhibition Using Virtual Screening and LEI Analysis.International journal of molecular sciences · 2021Article
- Functional interrogation and therapeutic targeting of protein tyrosine phosphatases.Biochemical Society transactions · 2021Review
- A screen of FDA-approved drugs identifies inhibitors of protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3).Scientific reports · 2021Article
- Structure of the Complex of an Iminopyridinedione Protein Tyrosine Phosphatase 4A3 Phosphatase Inhibitor with Human Serum Albumin.Molecular pharmacology · 2020Article
- Review
- PRL3 pseudophosphatase activity is necessary and sufficient to promote metastatic growth.The Journal of biological chemistry · 2020Article
- Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) drives migration and progression of T-cell acute lymphoblastic leukemia in vitro and in vivo.Oncogenesis · 2020Article
- Protein tyrosine phosphatases: promising targets in pancreatic ductal adenocarcinoma.Cellular and molecular life sciences : CMLS · 2019Review
- Optimal control nodes in disease-perturbed networks as targets for combination therapy.Nature communications · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphatase of regenerating liver (PRL) oncoproteins are phosphatases overexpressed in numerous types of human cancer. Elevated levels of PRL associate with metastasis and poor clinical outcomes. In principle, PRL phosphatases offer appealing therapeutic targets, but they remain underexplored due to the lack of specific chemical probes. In this study, we address this issue by exploiting a unique property of PRL phosphatases, namely, that they may function as homotrimers. Starting from a sequential structure-based virtual screening and medicinal chemistry strategy, we identified Cmpd-43 and several analogs that disrupt PRL1 trimerization. Biochemical and structural analyses demonstrate that Cmpd-43 and its close analogs directly bind the PRL1 trimer interface and obstruct PRL1 trimerization. Cmpd-43 also specifically blocks the PRL1-induced cell proliferation and migration through attenuation of both ERK1/2 and Akt activity. Importantly, Cmpd-43 exerted potent anticancer activity both in vitro and in vivo in a murine xenograft model of melanoma. Our results validate a trimerization-dependent signaling mechanism for PRL and offer proof of concept for trimerization inhibitors as candidate therapeutics to treat PRL-driven cancers. Cancer Res; 76(16); 4805-15. ©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.