Affiliation:
1. Department of Pharmacy, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China
2. College of Pharmacy, Gannan Medical University, Ganzhou, 341000, China
Abstract
Transthyretin (TTR) is associated with several human amyloid diseases. Various kinetic stabilizers have been developed to inhibit the dissociation of TTR tetramer and the formation of amyloid fibrils. Most of them are bisaryl derivatives, natural flavonoids, crown ethers and carborans. In this review article, we focus on TTR tetramer stabilizers, genetic therapeutic approaches and fibril remodelers. The binding modes of typical bisaryl derivatives, natural flavonoids, crown ethers and carborans are discussed. Based on knowledge of the binding of thyroxine to TTR tetramer, many stabilizers have been screened to dock into the thyroxine binding sites, leading to TTR tetramer stabilization. Particularly, those stabilizers with unique binding profiles have shown great potential in developing the therapeutic management of TTR amyloidogenesis.
Funder
National Natural Science Foundation of China
The National Science Foundation of Jiangxi Province
Innovative Teamwork Project of Gannan Medical University
Subject
Drug Discovery,Pharmacology,Molecular Medicine