ArticleChemMedChem2021
Heteroaromatic Inhibitors of the Astacin Proteinases Meprin α, Meprin β and Ovastacin Discovered by a Scaffold-Hopping Approach.
Article in ChemMedChem, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed, 14 citations in OpenAlex.
- Crossing the barrier or how regulation of ovastacin controls fertilization and translates into clinical phenotypes.iScience · 2025Review
- Astacin metalloproteases in human-parasitic nematodes.Advances in parasitology · 2024Review
- Synthesis and structure-activity relationships of pyrazole-based inhibitors of meprin α and β.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Structure and Dynamics of Meprin β in Complex with a Hydroxamate-Based Inhibitor.International journal of molecular sciences · 2021Article
- Heteroaromatic Inhibitors of the Astacin Proteinases Meprin α, Meprin β and Ovastacin Discovered by a Scaffold-Hopping Approach.ChemMedChem · 2021Article
- Discovery and Optimization of Selective Inhibitors of Meprin α (Part II).Pharmaceuticals (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Astacin metalloproteinases, in particular meprins α and β, as well as ovastacin, are emerging drug targets. Drug-discovery efforts have led to the development of the first potent and selective inhibitors in the last few years. However, the most recent compounds are based on a highly flexible tertiary amine scaffold that could cause metabolic liabilities or decreased potency due to the entropic penalty upon binding to the target. Thus, the aim of this study was to discover novel conformationally constrained scaffolds as starting points for further inhibitor optimization. Shifting from flexible tertiary amines to rigid heteroaromatic cores resulted in a boost in inhibitory activity. Moreover, some compounds already exhibited higher activity against individual astacin proteinases compared to recently reported inhibitors and also a favorable off-target selectivity profile, thus qualifying them as very suitable chemical probes for target validation.
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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.