ArticleNature communications2015
Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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
48 citing papers in PubMed, 95 citations in OpenAlex.
- IDE-mediated GLP-1 degradation as the basis for designing long-acting and CNS-stable GLP-1 receptor agonists.Science advances · 2026Article
- G3BP1 Succinylation at K413 is Critical for Cardiac Function by Modulating PI3K-AKT-mTOR Signal Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Click Reactions in Kinetic Target-Guided Synthesis: Progress in the Discovery of Inhibitors for Biological Targets.Methods and protocols · 2026Review
- It Takes Two to Tango: Current Understanding of the Role of M16 Family of Proteases and Their Structural Properties.Biomolecules · 2025Review
- Discovery of Boronic Acids-Based β-Lactamase Inhibitors Through In Situ Click Chemistry.International journal of molecular sciences · 2025Article
- Islet cell stress induced by insulin-degrading enzyme deficiency promotes regeneration and protection from autoimmune diabetes.iScience · 2024Article
- Insulin-degrading enzyme regulates insulin-directed cellular autoimmunity in murine type 1 diabetes.Frontiers in immunology · 2024Article
- Shotgun Kinetic Target-Guided Synthesis Approach Enables the Discovery of Small-Molecule Inhibitors against Pathogenic Free-Living Amoeba Glucokinases.ACS infectious diseases · 2023Article
- The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.Biomolecules · 2023Review
- Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins.Biomolecules · 2023Article
- Going beyond Binary: Rapid Identification of Protein-Protein Interaction Modulators Using a Multifragment Kinetic Target-Guided Synthesis Approach.Journal of medicinal chemistry · 2023Article
- Sirt3 deficiency induced down regulation of insulin degrading enzyme in comorbid Alzheimer's disease with metabolic syndrome.Scientific reports · 2022Article
- Discovery of the First Selective Nanomolar Inhibitors of ERAP2 by Kinetic Target-Guided Synthesis.Angewandte Chemie (International ed. in English) · 2022Article
- Exchange Broadening Underlies the Enhancement of IDE-Dependent Degradation of Insulin by Anionic Membranes.ACS omega · 2022Article
- Review
- Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition.Nature communications · 2022Article
- Inhibition of Insulin Degrading Enzyme to Control Diabetes Mellitus and its Applications on some Other Chronic Disease: a Critical Review.Pharmaceutical research · 2022Review
- Antibody-Mediated Inhibition of Insulin-Degrading Enzyme Improves Insulin Activity in a Diabetic Mouse Model.Frontiers in immunology · 2022Article
- Molecular Design in Practice: A Review of Selected Projects in a French Research Institute That Illustrates the Link between Chemical Biology and Medicinal Chemistry.Molecules (Basel, Switzerland) · 2021Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors at 6 institutions in 3 countries.
Funding
Abstract
Insulin-degrading enzyme (IDE) is a protease that cleaves insulin and other bioactive peptides such as amyloid-β. Knockout and genetic studies have linked IDE to Alzheimer's disease and type-2 diabetes. As the major insulin-degrading protease, IDE is a candidate drug target in diabetes. Here we have used kinetic target-guided synthesis to design the first catalytic site inhibitor of IDE suitable for in vivo studies (BDM44768). Crystallographic and small angle X-ray scattering analyses show that it locks IDE in a closed conformation. Among a panel of metalloproteases, BDM44768 selectively inhibits IDE. Acute treatment of mice with BDM44768 increases insulin signalling and surprisingly impairs glucose tolerance in an IDE-dependent manner. These results confirm that IDE is involved in pathways that modulate short-term glucose homeostasis, but casts doubt on the general usefulness of the inhibition of IDE catalytic activity to treat diabetes.
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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.