ArticleJournal of medicinal chemistry2013
Design, synthesis, and optimization of novel epoxide incorporating peptidomimetics as selective calpain inhibitors.
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 12 papers.
What it found
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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.
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
12 citing papers in PubMed, 35 citations in OpenAlex.
- Click chemistry for natural product-inspired covalent drug discovery.Drug discovery today · 2025Review
- Enzymatic combinatorial synthesis of E-64 and related cysteine protease inhibitors.Nature chemical biology · 2025Article
- Extending the Calpain-Cathepsin Hypothesis to the Neurovasculature: Protection of Brain Endothelial Cells and Mice from Neurotrauma.ACS pharmacology & translational science · 2021Article
- Synthesis of α-Ketoamide-Based Stereoselective Calpain-1 Inhibitors as Neuroprotective Agents.ChemMedChem · 2020Article
- Catch and Release Photosensitizers: Combining Dual-Action Ruthenium Complexes with Protease Inactivation for Targeting Invasive Cancers.Journal of the American Chemical Society · 2018Article
- Mitigating the Metabolic Liability of Carbonyl Reduction: Novel Calpain Inhibitors with P1' Extension.ACS medicinal chemistry letters · 2018Article
- Covalent Tethering of Fragments For Covalent Probe Discovery.MedChemComm · 2016Article
- Novel Selective Calpain 1 Inhibitors as Potential Therapeutics in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2016Article
- Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors.Acta pharmaceutica Sinica. B · 2015Review
- Epoxide based inhibitors of the hepatitis C virus non-structural 2 autoprotease.Antiviral research · 2015Article
- Synaptic therapy in Alzheimer's disease: a CREB-centric approach.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2015Review
- Cathepsin B is a New Drug Target for Traumatic Brain Injury Therapeutics: Evidence for E64d as a Promising Lead Drug Candidate.Frontiers in neurology · 2015Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Hyperactivation of the calcium-dependent cysteine protease calpain 1 (Cal1) is implicated as a primary or secondary pathological event in a wide range of illnesses and in neurodegenerative states, including Alzheimer's disease (AD). E-64 is an epoxide-containing natural product identified as a potent nonselective, calpain inhibitor, with demonstrated efficacy in animal models of AD. By use of E-64 as a lead, three successive generations of calpain inhibitors were developed using computationally assisted design to increase selectivity for Cal1. First generation analogues were potent inhibitors, effecting covalent modification of recombinant Cal1 catalytic domain (Cal1cat), demonstrated using LC-MS/MS. Refinement yielded second generation inhibitors with improved selectivity. Further library expansion and ligand refinement gave three Cal1 inhibitors, one of which was designed as an activity-based protein profiling probe. These were determined to be irreversible and selective inhibitors by kinetics studies comparing full length Cal1 with the general cysteine protease papain.
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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.