ArticleJournal of medicinal chemistry2013
Optimization of peptide hydroxamate inhibitors of insulin-degrading enzyme reveals marked substrate-selectivity.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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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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
34 citing papers in PubMed, 60 citations in OpenAlex.
- It Takes Two to Tango: Current Understanding of the Role of M16 Family of Proteases and Their Structural Properties.Biomolecules · 2025Review
- The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.Biomolecules · 2023Review
- Exchange Broadening Underlies the Enhancement of IDE-Dependent Degradation of Insulin by Anionic Membranes.ACS omega · 2022Article
- Molecular Modeling and Phenotypic Description of a Patient with a Novel Exonic Deletion ofMolecular syndromology · 2022Article
- Inhibition of Insulin Degrading Enzyme to Control Diabetes Mellitus and its Applications on some Other Chronic Disease: a Critical Review.Pharmaceutical research · 2022Review
- Article
- Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme.Antioxidants (Basel, Switzerland) · 2021Article
- Hydroxypyridinethione Inhibitors of Human Insulin-Degrading Enzyme.ChemMedChem · 2021Article
- Attacking COVID-19 Progression Using Multi-Drug Therapy for Synergetic Target Engagement.Biomolecules · 2021Article
- Targeting Insulin-Degrading Enzyme in Insulin Clearance.International journal of molecular sciences · 2021Review
- Quantitative, High-Throughput Assays for Proteolytic Degradation of Amylin.Methods and protocols · 2020Article
- Computational design of substrate selective inhibition.PLoS computational biology · 2020Article
- Examination of Molecular Effects ofCase reports in medicine · 2020Article
- Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling.Case reports in genetics · 2020Article
- Genomic Observations of a Rare/PathogenicMedicina (Kaunas, Lithuania) · 2019Article
- Protein informatics combined with multiple data sources enriches the clinical characterization of novel TRPV4 variant causing an intermediate skeletal dysplasia.Molecular genetics & genomic medicine · 2019Article
- Development and Characterization of Quantitative, High-Throughput-Compatible Assays for Proteolytic Degradation of Glucagon.SLAS discovery : advancing life sciences R & D · 2018Article
- Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data?Molecules (Basel, Switzerland) · 2018Article
- Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: link between type 2 diabetes and Alzheimer's disease.Drug design, development and therapy · 2018Review
- Peptidic inhibitors of insulin-degrading enzyme with potential for dermatological applications discovered via phage display.PloS one · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin-degrading enzyme (IDE) is an atypical zinc-metallopeptidase that degrades insulin and the amyloid ß-protein and is strongly implicated in the pathogenesis of diabetes and Alzheimer's disease. We recently developed the first effective inhibitors of IDE, peptide hydroxamates that, while highly potent and selective, are relatively large (MW > 740) and difficult to synthesize. We present here a facile synthetic route that yields enantiomerically pure derivatives comparable in potency to the parent compounds. Through the generation of truncated variants, we identified a compound with significantly reduced size (MW = 455.5) that nonetheless retains good potency (ki = 78 ± 11 nM) and selectivity for IDE. Notably, the potency of these inhibitors was found to vary as much as 60-fold in a substrate-specific manner, an unexpected finding for active site-directed inhibitors. Collectively, our findings demonstrate that potent, small-molecule IDE inhibitors can be developed that, in certain instances, can be highly substrate selective.
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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.