ArticleJournal of natural products2014
The marine cyanobacterial metabolite gallinamide A is a potent and selective inhibitor of human cathepsin L.
Article in Journal of natural products, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Cathepsin B-Oriented Screening, Isolation, and Antitumor Validation of Bioactive Metabolites fromMarine drugs · 2026Article
- Marine Cyanobacteria: A Rich Source of Structurally Unique Anti-Infectives for Drug Development.Molecules (Basel, Switzerland) · 2024Review
- Metabolomic Analysis and Antiviral Screening of a Marine Algae Library Yield Jobosic Acid (2,5-Dimethyltetradecanoic Acid) as a Selective Inhibitor of SARS-CoV-2.Journal of natural products · 2024Article
- Nature-Inspired Gallinamides Are Potent Antischistosomal Agents: Inhibition of the Cathepsin B1 Protease Target and Binding Mode Analysis.ACS infectious diseases · 2024Article
- Role of marine natural products in the development of antiviral agents against SARS-CoV-2: potential and prospects.Marine life science & technology · 2024Review
- Computational Approaches to Enzyme Inhibition by Marine Natural Products in the Search for New Drugs.Marine drugs · 2023Review
- Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022Review
- The Key Role of Lysosomal Protease Cathepsins in Viral Infections.International journal of molecular sciences · 2022Review
- Native metabolomics identifies the rivulariapeptolide family of protease inhibitors.Nature communications · 2022Article
- Discovery of pH-Selective Marine and Plant Natural Product Inhibitors of Cathepsin B Revealed by Screening at Acidic and Neutral pH Conditions.ACS omega · 2022Article
- Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L.Journal of medicinal chemistry · 2022Article
- Bioactive natural products in COVID-19 therapy.Frontiers in pharmacology · 2022Review
- Natural Products with Potential to Treat RNA Virus Pathogens Including SARS-CoV-2.Journal of natural products · 2021Review
- Azanitrile Inhibitors of the SmCB1 Protease Target Are Lethal toACS infectious diseases · 2021Article
- Natural Bioactive Molecules as Potential Agents Against SARS-CoV-2.Frontiers in pharmacology · 2021Review
- Targeting eukaryotic proteases for natural products-based drug development.Natural product reports · 2020Review
- The Biological and Chemical Diversity of Tetramic Acid Compounds from Marine-Derived Microorganisms.Marine drugs · 2020Review
- A Review of Small Molecule Inhibitors and Functional Probes of Human Cathepsin L.Molecules (Basel, Switzerland) · 2020Review
- Biologically active compounds from marine organisms in the strategies for combating coronaviruses.AIMS microbiology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
A number of marine natural products are potent inhibitors of proteases, an important drug target class in human diseases. Hence, marine cyanobacterial extracts were assessed for inhibitory activity to human cathepsin L. Herein, we have shown that gallinamide A potently and selectively inhibits the human cysteine protease cathepsin L. With 30 min of preincubation, gallinamide A displayed an IC50 of 5.0 nM, and kinetic analysis demonstrated an inhibition constant of ki = 9000 ± 260 M(-1) s(-1). Preincubation-dilution and activity-probe experiments revealed an irreversible mode of inhibition, and comparative IC50 values display a 28- to 320-fold greater selectivity toward cathepsin L than closely related human cysteine cathepsin V or B. Molecular docking and molecular dynamics simulations were used to determine the pose of gallinamide in the active site of cathepsin L. These data resulted in the identification of a pose characterized by high stability, a consistent hydrogen bond network, and the reactive Michael acceptor enamide of gallinamide A positioned near the active site cysteine of the protease, leading to a proposed mechanism of covalent inhibition. These data reveal and characterize the novel activity of gallinamide A as a potent inhibitor of human cathepsin L.
Indexed as
Identifiers
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.