ArticleNature communications2016
Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 83 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
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 citations in OpenAlex.
- Pharmacological treatment for familial amyloid polyneuropathy.The Cochrane database of systematic reviews · 2020Pooled it
- Synthesis, Structural Characterization, and In Silico Evaluation of the Salicylidene Schiff Base 4‑{(ACS omega · 2026Article
- Mass spectrometry footprinting reveals how kinetic stabilizers counteract transthyretin dynamics altered by pathogenic mutations.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Antimicrobial Peptides as Cross-Seeding Modulators at the Neurodegenerative-Infectious Interface.Research (Washington, D.C.) · 2026Review
- Case Report: Five-year follow-up of leptomeningeal transthyretin amyloidosis (Ala45Thr) with CNS involvement under tolcapone therapy.Frontiers in medicine · 2026Article
- Transthyretin cardiac amyloidosis: advances and ambiguities.Heart failure reviews · 2025Review
- Engineering of an Fc-specific monovalent protein G for the light-controlled affinity purification of antibodies.Scientific reports · 2025Article
- In vitro and in vivo disease models of cardiac amyloidosis: progress, pitfalls, and potential.Cardiovascular research · 2025Review
- Differentiating the solution structures and stability of transthyretin tetramer complexed with tolcapone and tafamidis using SEC-SWAXS and NMR.Journal of applied crystallography · 2025Article
- Uncovering cell type-specific phenotypes using a novel human in vitro model of transthyretin amyloid cardiomyopathy.Stem cell research & therapy · 2025Article
- Clinical and Biochemical Characterization of Hereditary ATTR Amyloidosis Caused by a Novel Transthyretin Variant V121A (p.V141A).International journal of molecular sciences · 2025Article
- Disease-modifying therapies for amyloid transthyretin cardiomyopathy: Current and emerging medications.Pharmacotherapy · 2025Review
- Transthyretin Cardiac Amyloidosis: Current and Emerging Therapies.Current cardiology reports · 2025Review
- Divergent Total Synthesis of Isoflavone Natural Products and Their Potential as Therapeutic Agents for TTR Amyloidosis.Journal of natural products · 2024Article
- A Snapshot of the Most Recent Transthyretin Stabilizers.International journal of molecular sciences · 2024Review
- Early Diagnosis of Amyloidosis and Cardiac Involvement through Carpal Tunnel Surgery and Predictive Factors.Journal of clinical medicine · 2024Article
- Tafamidis therapy in transthyretin amyloid cardiomyopathy: a narrative review from clinical trials and real-world evidence.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- Development of Benziodarone Analogues with Enhanced Potency for Selective Binding to Transthyretin in Human Plasma.Journal of medicinal chemistry · 2024Article
- NRhFluors: Quantitative Revealing the Interaction between Protein Homeostasis and Mitochondria Dysfunction via Fluorescence Lifetime Imaging.ACS central science · 2024Article
- Synthesis and PET Imaging Biodistribution Studies of Radiolabeled Iododiflunisal, a Transthyretin Tetramer Stabilizer, Candidate Drug for Alzheimer's Disease.Molecules (Basel, Switzerland) · 2024Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological TTR aggregation. Native state stabilizers are promising drugs to treat TTR amyloidoses. Here we repurpose tolcapone, an FDA-approved molecule for Parkinson's disease, as a potent TTR aggregation inhibitor. Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. These data indicate that tolcapone, already in clinical trials for familial amyloid polyneuropathy, is a strong candidate for therapeutic intervention in these diseases, including those affecting the central nervous system, for which no small-molecule therapy exists.
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.