ArticleEuropean journal of medicinal chemistry2015
Structure-activity relationships of imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human insulin-degrading enzyme.
Article in European journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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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
10 citing papers in PubMed, 29 citations in OpenAlex.
- It Takes Two to Tango: Current Understanding of the Role of M16 Family of Proteases and Their Structural Properties.Biomolecules · 2025Review
- Review
- Controllable preparation and performance of bio-based poly(lactic acid-iminodiacetic acid) as sustained-release PbiScience · 2021Article
- Hydroxypyridinethione Inhibitors of Human Insulin-Degrading Enzyme.ChemMedChem · 2021Article
- Antiproliferative Activity of Functionalized Histidine-derived Au(I) bis-NHC Complexes for Bioconjugation.Chemistry, an Asian journal · 2020Article
- Identification of ebselen as a potent inhibitor of insulin degrading enzyme by a drug repurposing screening.European journal of medicinal chemistry · 2019Article
- Peptidic inhibitors of insulin-degrading enzyme with potential for dermatological applications discovered via phage display.PloS one · 2018Article
- Crystal Structure and Function of PqqF Protein in the Pyrroloquinoline Quinone Biosynthetic Pathway.The Journal of biological chemistry · 2016Article
- Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus.Trends in endocrinology and metabolism: TEM · 2016Review
- Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme.Journal of molecular biology · 2015Article
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
Abstract
Insulin degrading enzyme (IDE) is a zinc metalloprotease that degrades small amyloid peptides such as amyloid-â and insulin. So far the dearth of IDE-specific pharmacological inhibitors impacts the understanding of its role in the physiopathology of Alzheimer's disease, amyloid-â clearance, and its validation as a potential therapeutic target. Hit 1 was previously discovered by high-throughput screening. Here we describe the structure-activity study, that required the synthesis of 48 analogues. We found that while the carboxylic acid, the imidazole and the tertiary amine were critical for activity, the methyl ester was successfully optimized to an amide or a 1,2,4-oxadiazole. Along with improving their activity, compounds were optimized for solubility, lipophilicity and stability in plasma and microsomes. The docking or co-crystallization of some compounds at the exosite or the catalytic site of IDE provided the structural basis for IDE inhibition. The pharmacokinetic properties of best compounds 44 and 46 were measured in vivo. As a result, 44 (BDM43079) and its methyl ester precursor 48 (BDM43124) are useful chemical probes for the exploration of IDE's role.
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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.