Journal Article

Small molecules as transthyretin stabilizers in cardiac amyloidosis: a short review of recent advances

Uspenskaya, Mayya V., Olekhnovich, Roman O., Elangwe, Collins N., Samuilova, Evgenia O.

2026

Overview

Recent advances in therapeutic strategies have emerged to address transthyretin-related amyloidosis, a progressive disorder characterized by diverse clinical manifestations including cardiomyopathy and polyneuropathy. Cardiac amyloidosis (CA), resulting from myocardial amyloid fibril deposition, induces restrictive cardiomyopathy and severe diastolic dysfunction. Among current treatment modalities, transthyretin (TTR) stabilizers have become therapeutic cornerstones, exemplified by the clinical implementation of tafamidis and ongoing trials with acoramidis. Nevertheless, persistent challenges in disease management necessitate the development of improved therapeutics. Notably, natural compounds have gained prominence as promising candidates for developing safer, less toxic TTR stabilizers that may overcome limitations of existing synthetic drugs. This review critically evaluates the most promising recently reported TTR stabilizers, with particular emphasis on natural products and their derivatives as innovative alternatives to conventional synthetic stabilizers.