ArticleProceedings of the National Academy of Sciences of the United States of America2011
Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 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
64 citing papers in PubMed, 106 citations in OpenAlex.
- HIF-1-mediated PPME1 expression promotes breast cancer progression via AKT activation and β-catenin recruitment.The Journal of clinical investigation · 2026Article
- Identification of Pyrazolidine-3-One Derivatives as a Novel Structural Scaffold for ATP Synthase Inhibitors.ChemMedChem · 2026Article
- Catalytic Serine Labeling in Nonaqueous, Acidic Media.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Chemical proteomic mapping of reversible small molecule binding sites in native systems.Trends in pharmacological sciences · 2024Review
- Biomarkers and Target-Specific Small-Molecule Drugs in Alzheimer's Diagnostic and Therapeutic Research: From Amyloidosis to Tauopathy.Neurochemical research · 2024Review
- Inhibitors of the Thioesterase Activity ofACS infectious diseases · 2024Article
- Mapping the Evolution of Activity-Based Protein Profiling: A Bibliometric Review.Advanced pharmaceutical bulletin · 2023Article
- Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules.The Journal of biological chemistry · 2022Review
- Article
- PP2A and Its Inhibitors in Helper T-Cell Differentiation and Autoimmunity.Frontiers in immunology · 2021Review
- Taurine Antagonizes Macrophages M1 Polarization by Mitophagy-Glycolysis Switch BlockageFrontiers in immunology · 2021Article
- Effects of carboxyl-terminal methylation on holoenzyme function of the PP2A subfamily.Biochemical Society transactions · 2020Review
- Methionine-Mediated Protein Phosphatase 2A Catalytic Subunit (PP2Ac) Methylation Ameliorates the Tauopathy Induced by Manganese in Cell and Animal Models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
- Reduced Expression of the PP2A Methylesterase, PME-1, or the PP2A Methyltransferase, LCMT-1, Alters Sensitivity to Beta-Amyloid-Induced Cognitive and Electrophysiological Impairments in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling.Cellular and molecular life sciences : CMLS · 2019Review
- PP2A: A Promising Biomarker and Therapeutic Target in Endometrial Cancer.Frontiers in oncology · 2019Review
- Chemical probes and drug leads from advances in synthetic planning and methodology.Nature reviews. Drug discovery · 2018Review
- Therapeutic targeting of PP2A.The international journal of biochemistry & cell biology · 2018Review
- Advanced Activity-Based Protein Profiling Application Strategies for Drug Development.Frontiers in pharmacology · 2018Review
- Activity-based protein profiling for mapping and pharmacologically interrogating proteome-wide ligandable hotspots.Current opinion in biotechnology · 2017Review
4 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
14 authors at 2 institutions in 1 country.
Funding
Abstract
National Institutes of Health (NIH)-sponsored screening centers provide academic researchers with a special opportunity to pursue small-molecule probes for protein targets that are outside the current interest of, or beyond the standard technologies employed by, the pharmaceutical industry. Here, we describe the outcome of an inhibitor screen for one such target, the enzyme protein phosphatase methylesterase-1 (PME-1), which regulates the methylesterification state of protein phosphatase 2A (PP2A) and is implicated in cancer and neurodegeneration. Inhibitors of PME-1 have not yet been described, which we attribute, at least in part, to a dearth of substrate assays compatible with high-throughput screening. We show that PME-1 is assayable by fluorescence polarization-activity-based protein profiling (fluopol-ABPP) and use this platform to screen the 300,000+ member NIH small-molecule library. This screen identified an unusual class of compounds, the aza-β-lactams (ABLs), as potent (IC(50) values of approximately 10 nM), covalent PME-1 inhibitors. Interestingly, ABLs did not derive from a commercial vendor but rather an academic contribution to the public library. We show using competitive-ABPP that ABLs are exquisitely selective for PME-1 in living cells and mice, where enzyme inactivation leads to substantial reductions in demethylated PP2A. In summary, we have combined advanced synthetic and chemoproteomic methods to discover a class of ABL inhibitors that can be used to selectively perturb PME-1 activity in diverse biological systems. More generally, these results illustrate how public screening centers can serve as hubs to create spontaneous collaborative opportunities between synthetic chemistry and chemical biology labs interested in creating first-in-class pharmacological probes for challenging protein targets.
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.