ArticleJournal of medicinal chemistry2018
Enthalpy-Driven Stabilization of Transthyretin by AG10 Mimics a Naturally Occurring Genetic Variant That Protects from Transthyretin Amyloidosis.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 95 citations in OpenAlex.
- Long-Term Efficacy and Safety of Acoramidis in ATTR-CM: Initial Report From the Open-Label Extension of the ATTRibute-CM Trial.Circulation · 2025Trial
- First-in-Human Study of AG10, a Novel, Oral, Specific, Selective, and Potent Transthyretin Stabilizer for the Treatment of Transthyretin Amyloidosis: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Adult Volunteers.Clinical pharmacology in drug development · 2020Trial
- ACO-SWITCH: Rationale and Design of a Phase 4 Study Evaluating Serum Transthyretin in ATTR-CM After Switching from Tafamidis to Acoramidis.Cardiology and therapy · 2026Article
- Rationale and Design of ACO-REAL: A Real-World Non-Interventional Study of Acoramidis in Routine Clinical Practice.Cardiology and therapy · 2026Article
- Differential Transthyretin Stabilization in Patients With Wild Type and Variant Transthyretin Amyloidosis.JACC. CardioOncology · 2026Article
- Evaluation of the Current ATTR-CM Treatment Landscape via a Mathematical Model of TTR Dissociation and Amyloid Formation.CPT: pharmacometrics & systems pharmacology · 2026Article
- Acoramidis in transthyretin amyloid cardiomyopathy: expanding evidence from ATTRibute-CM.Future cardiology · 2026Review
- Phenomenological model of transthyretin stabilization.Scientific reports · 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
- Unravelling the myriad physiologic roles of transthyretin: critical considerations for treating transthyretin amyloidosis.Annals of medicine · 2025Review
- Transthyretin Kinetic Stabilizers for ATTR Amyloidosis.Cardiology and therapy · 2025Article
- Transthyretin Amyloid Cardiomyopathy Treatment: An Updated Review.Journal of clinical medicine · 2025Review
- Transthyretin Amyloid Cardiomyopathy-2025 Update: Current Diagnostic Approaches and Emerging Therapeutic Options.Journal of clinical medicine · 2025Review
- Differential Binding Affinities and Kinetics of Transthyretin Stabilizers.Journal of cardiovascular pharmacology · 2025Article
- Acoramidis: First Approval.Drugs · 2025Review
- Pharmacological Management of Transthyretin Amyloid Cardiomyopathy: Where We Are and Where We Are Going.Journal of clinical medicine · 2025Review
- Highlights on U.S. FDA-approved halogen-containing drugs in 2024.European journal of medicinal chemistry · 2025Review
- Evolving Strategies in Cardiac Amyloidosis: From Mechanistic Discoveries to Diagnostic and Therapeutic Advances.Cardiology clinics · 2025Review
- A Snapshot of the Most Recent Transthyretin Stabilizers.International journal of molecular sciences · 2024Review
- Development of Benziodarone Analogues with Enhanced Potency for Selective Binding to Transthyretin in Human Plasma.Journal of medicinal chemistry · 2024Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a fatal disease with no available disease-modifying therapies. While pathogenic TTR mutations (TTRm) destabilize TTR tetramers, the T119M variant stabilizes TTRm and prevents disease. A comparison of potency for leading TTR stabilizers in clinic and structural features important for effective TTR stabilization is lacking. Here, we found that molecular interactions reflected in better binding enthalpy may be critical for development of TTR stabilizers with improved potency and selectivity. Our studies provide mechanistic insights into the unique binding mode of the TTR stabilizer, AG10, which could be attributed to mimicking the stabilizing T119M variant. Because of the lack of animal models for ATTR-CM, we developed an in vivo system in dogs which proved appropriate for assessing the pharmacokinetics-pharmacodynamics profile of TTR stabilizers. In addition to stabilizing TTR, we hypothesize that optimizing the binding enthalpy could have implications for designing therapeutic agents for other amyloid diseases.
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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.