ArticleNature chemical biology2014
Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.
- The role of PPM1D in cancer and advances in studies of its inhibitors.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020Pooled it
- Unleashing the power of DNA-encoded libraries for challenging targets in drug discovery.Pharmaceutical science advances · 2026Review
- Combined inhibition of PLK4 and PPM1D promotes cell death in cancer cells with 17q amplification.Cancer cell international · 2026Article
- KDM4D enhances radiosensitivity in esophageal squamous cell carcinoma through the SRBD1/RPL11/c-Myc/WIP1/CHK1 axis.American journal of translational research · 2026Article
- PPM1D is directly degraded by proteasomes in a ubiquitination-independent manner through its carboxyl-terminal region.Journal of biomedical science · 2025Article
- WIP1 mutations suppress DNA damage triggered bypass of the mitotic timer.The EMBO journal · 2025Article
- Cell confluency affects p53 dynamics in response to DNA damage.Molecular biology of the cell · 2025Article
- An ATM-PPM1D Circuit Controls the Processing and Restart of DNA Replication Forks.bioRxiv : the preprint server for biology · 2025Article
- Identification of small molecule inhibitors of PPM1D using an integrated drug discovery platform.iScience · 2025Article
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- PPM1D activity promotes cellular transformation by preventing senescence and cell death.Oncogene · 2024Article
- Docking interactions determine substrate specificity of members of a widespread family of protein phosphatases.The Journal of biological chemistry · 2024Article
- Dual-Action Kinase Inhibitors Influence p38α MAP Kinase Dephosphorylation.bioRxiv : the preprint server for biology · 2024Article
- Hematopoietic stem cell fate under the influence of Ser/Thr protein phosphatases.Haematologica · 2024Article
- Building Block-Centric Approach to DNA-Encoded Library Design.Journal of chemical information and modeling · 2024Article
- Identification of Small Molecule Inhibitors of PPM1D Using a Novel Drug Discovery Platform.bioRxiv : the preprint server for biology · 2024Article
- Control of cell proliferation by memories of mitosis.Science (New York, N.Y.) · 2024Article
- Toward physics-based precision medicine: Exploiting protein dynamics to design new therapeutics and interpret variants.Protein science : a publication of the Protein Society · 2024Review
44 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
27 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although therapeutic interventions of signal-transduction cascades with targeted kinase inhibitors are a well-established strategy, drug-discovery efforts to identify targeted phosphatase inhibitors have proven challenging. Herein we report a series of allosteric, small-molecule inhibitors of wild-type p53-induced phosphatase (Wip1), an oncogenic phosphatase common to multiple cancers. Compound binding to Wip1 is dependent on a 'flap' subdomain located near the Wip1 catalytic site that renders Wip1 structurally divergent from other members of the protein phosphatase 2C (PP2C) family and that thereby confers selectivity for Wip1 over other phosphatases. Treatment of tumor cells with the inhibitor GSK2830371 increases phosphorylation of Wip1 substrates and causes growth inhibition in both hematopoietic tumor cell lines and Wip1-amplified breast tumor cells harboring wild-type TP53. Oral administration of Wip1 inhibitors in mice results in expected pharmacodynamic effects and causes inhibition of lymphoma xenograft growth. To our knowledge, GSK2830371 is the first orally active, allosteric inhibitor of Wip1 phosphatase.
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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.