BROWSE

Related Scientist

Ko, Young Ho's photo.

Ko, Young Ho
복잡계 자기조립 연구단
more info

ITEM VIEW & DOWNLOAD

Diphenyl-methane based thyromimetic inhibitors for transthyretin amyloidosis

Cited 0 time in webofscience Cited 0 time in scopus
16 Viewed 0 Downloaded
Title
Diphenyl-methane based thyromimetic inhibitors for transthyretin amyloidosis
Author(s)
Kim, Bokyung; Young Ho Ko; Runfola, Massimiliano; Rapposelli, Simona; Ortore, Gabriella; Chiellini, Grazia; Kim, Jin Hae
Publication Date
2021-04
Journal
International Journal of Molecular Sciences, v.22, no.7
Publisher
MDPI AG
Abstract
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thy-romimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simula-tion, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thy-romimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.
URI
https://pr.ibs.re.kr/handle/8788114/9595
DOI
10.3390/ijms22073488
ISSN
1661-6596
Appears in Collections:
Center for Self-assembly and Complexity(복잡계 자기조립 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
There are no files associated with this item.

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse