ArticleNature chemical biology2014
A high-throughput, multiplexed assay for superfamily-wide profiling of enzyme activity.
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 42 papers.
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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.
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Who cites it
42 citing papers in PubMed.
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- Acylamino acid-releasing enzyme, a bifunctional protease with a potential role in aging.Journal of experimental botany · 2025Review
- The multifunctional regulatory post-proline protease dipeptidyl peptidase 9 and its inhibitors: new opportunities for therapeutics.Cellular and molecular life sciences : CMLS · 2025Review
- Human genetics identify convergent signals in mitochondrial LACTB-mediated lipid metabolism in cardiovascular-kidney-metabolic syndrome.Cell metabolism · 2025Article
- Ligand discovery by activity-based protein profiling.Cell chemical biology · 2024Review
- Activity-based protein profiling - finding general solutions to specific problems.Israel journal of chemistry · 2023Article
- DPP8/9 are not Required to Cleave Most Proline-Containing Peptides.Israel journal of chemistry · 2023Article
- A deeply conserved protease, acylamino acid-releasing enzyme (AARE), acts in ageing in Physcomitrella and Arabidopsis.Communications biology · 2023Article
- Induction of pyroptotic cell death as a potential tool for cancer treatment.Journal of inflammation (London, England) · 2022Review
- Identification of Sclareol As a Natural Neuroprotective CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- NLRP1 Inflammasomes: A Potential Target for the Treatment of Several Types of Brain Injury.Frontiers in immunology · 2022Review
- The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic.Nature reviews. Endocrinology · 2020Review
- Design of Optical-Imaging Probes by Screening of Diverse Substrate Libraries Directly in Disease-Tissue Extracts.Angewandte Chemie (International ed. in English) · 2020Article
- Direct Antiviral Treatments for Hepatitis C Virus Have Off-Target Effects of Oncologic Relevance in Hepatocellular Carcinoma.Cancers · 2020Article
- The NLRP1 and CARD8 inflammasomes.Immunological reviews · 2020Review
- Article
- High-Resolution Confocal Fluorescence Imaging of Serine Hydrolase Activity in Cryosections - Application to Glioma Brain Unveils Activity Hotspots Originating from Tumor-Associated Neutrophils.Biological procedures online · 2020Article
- Comparative analysis of the human serine hydrolase OVCA2 to the model serine hydrolase homolog FSH1 from S. cerevisiae.PloS one · 2020Article
- 6-Substituted amiloride derivatives as inhibitors of the urokinase-type plasminogen activator for use in metastatic disease.Bioorganic & medicinal chemistry letters · 2019Article
- DPP9's Enzymatic Activity and Not Its Binding to CARD8 Inhibits Inflammasome Activation.ACS chemical biology · 2019Article
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Abstract
The selectivity of an enzyme inhibitor is a key determinant of its usefulness as a tool compound or its safety as a drug. Yet selectivity is never assessed comprehensively in the early stages of the drug discovery process, and only rarely in the later stages, because technical limitations prohibit doing otherwise. Here, we report EnPlex, an efficient, high-throughput method for simultaneously assessing inhibitor potency and specificity, and pilot its application to 96 serine hydrolases. EnPlex analysis of widely used serine hydrolase inhibitors revealed numerous previously unrecognized off-target interactions, some of which may help to explain previously confounding adverse effects. In addition, EnPlex screening of a hydrolase-directed library of boronic acid- and nitrile-containing compounds provided structure-activity relationships in both potency and selectivity dimensions from which lead candidates could be more effectively prioritized. Follow-up of a series of dipeptidyl peptidase 4 inhibitors showed that EnPlex indeed predicted efficacy and safety in animal models. These results demonstrate the feasibility and value of high-throughput, superfamily-wide selectivity profiling and suggest that such profiling can be incorporated into the earliest stages of drug discovery.
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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.