ArticleEuropean journal of medicinal chemistry2014
Biochemical evaluation of virtual screening methods reveals a cell-active inhibitor of the cancer-promoting phosphatases of regenerating liver.
Article in European journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
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- Discovery of inhibitors of the cancer-promoting phosphatase PRL-3 and their evaluation in intestinal organoids.Bioorganic & medicinal chemistry · 2025Article
- Hypershape Recognition: A General Framework for Moment-Based Molecular Similarity.Journal of chemical information and modeling · 2025Article
- Rag2Mol: structure-based drug design based on retrieval augmented generation.Briefings in bioinformatics · 2025Article
- In silico identification of putative druggable pockets in PRL3, a significant oncology target.Biochemistry and biophysics reports · 2024Article
- Comprehensive machine learning boosts structure-based virtual screening for PARP1 inhibitors.Journal of cheminformatics · 2024Article
- Targeting Moonlighting Enzymes in Cancer.Molecules (Basel, Switzerland) · 2024Review
- Targeting PRL phosphatases in hematological malignancies.Expert opinion on therapeutic targets · 2024Review
- Graph neural networks are promising for phenotypic virtual screening on cancer cell lines.Biology methods & protocols · 2024Article
- PRL3 as a therapeutic target for novel cancer immunotherapy in multiple cancer types.Theranostics · 2023Review
- Article
- The phosphatase PRL-3 affects intestinal homeostasis by altering the crypt cell composition.Journal of molecular medicine (Berlin, Germany) · 2021Article
- A screen of FDA-approved drugs identifies inhibitors of protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3).Scientific reports · 2021Article
- Synthesis and vinyl benzene copolymerization of novel trisubstituted ethylenes: 15. Halogen and methoxy ring-substituted isopropyl 2-cyano-3-phenyl-2-propenoates.Designed monomers and polymers · 2020Article
- Turn and Face the Strange: A New View on Phosphatases.ACS central science · 2020Review
- Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) drives migration and progression of T-cell acute lymphoblastic leukemia in vitro and in vivo.Oncogenesis · 2020Article
- Next-Generation Cell-Active Inhibitors of the Undrugged Oncogenic PTP4A3 Phosphatase.The Journal of pharmacology and experimental therapeutics · 2019Article
- Protein tyrosine phosphatases: promising targets in pancreatic ductal adenocarcinoma.Cellular and molecular life sciences : CMLS · 2019Review
- Mechanism of thienopyridone and iminothienopyridinedione inhibition of protein phosphatases.MedChemComm · 2019Article
- Shape similarity guided pose prediction: lessons from D3R Grand Challenge 3.Journal of computer-aided molecular design · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
Computationally supported development of small molecule inhibitors has successfully been applied to protein tyrosine phosphatases in the past, revealing a number of cell-active compounds. Similar approaches have also been used to screen for small molecule inhibitors for the cancer-related phosphatases of regenerating liver (PRL) family. Still, selective and cell-active compounds are of limited availability. Since especially PRL-3 remains an attractive drug target due to its clear role in cancer metastasis, such compounds are highly demanded. In this study, we investigated various virtual screening approaches for their applicability to identify novel small molecule entities for PRL-3 as target. Biochemical evaluation of purchasable compounds revealed ligand-based approaches as well suited for this target, compared to docking-based techniques that did not perform well in this context. The best hit of this study, a 2-cyano-2-ene-ester and hence a novel chemotype targeting the PRLs, was further optimized by a structure-activity-relationship (SAR) study, leading to a low micromolar PRL inhibitor with acceptable selectivity over other protein tyrosine phosphatases. The compound is active in cells, as shown by its ability to specifically revert PRL-3 induced cell migration, and exhibits similar effects on PRL-1 and PRL-2. It is furthermore suitable for fluorescence microscopy applications, and it is commercially available. These features make it the only purchasable, cell-active and acceptably selective PRL inhibitor to date that can be used in various cellular applications.
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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.