9JIR

Crystal structure of V30M-TTR in complex with ioxynil

これはPDB形式変換不可エントリーです。

9JIR の概要

• エントリーDOI: 10.2210/pdb9jir/pdb
• 分子名称: Transthyretin, ioxynil (3 entities in total)
• 機能のキーワード: amyloidosis, tyroxine, inhibitor, stabilizer, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35797.91

構造登録者

Yokoyama, T. (登録日: 2024-09-12, 公開日: 2025-01-22, 最終更新日: 2025-02-05)

主引用文献

Yokoyama, T.,Fujiwara, S.,Nishikubo, K.,Mizuguchi, M.,Nabeshima, Y.,Toyooka, N.,Okada, T.,Nakagawa, Y.
Repurposing of Agrochemicals as ATTRv Amyloidosis Inhibitors.
J.Med.Chem., 68:1572-1586, 2025

PubMed Abstract: Transthyretin (TTR), a plasma protein, undergoes transformation into amyloid fibers, leading to ATTRv amyloidosis, a disease characterized by organ deposition of TTR amyloid fibrils and subsequent organ failure. Developing compounds that bind and kinetically stabilize TTR is a crucial strategy in the treatment of ATTRv amyloidosis. In this study, we narrowed 651 pesticide-related compounds down to 14 possible TTR binders through in silico screening; subsequent in vitro analysis revealed that 7 of them exhibited amyloid fibril formation inhibition activity. The herbicide components bromoxynil () and ioxynil () showed especially high ligand efficiency and efficiently inhibited amyloid fibril formation of amyloidogenic V30M-TTR. Additionally, aclonifen () exhibited moderate fibril formation inhibition activity, but showed selective binding to TTR comparable to that of tafamidis. While improvement is needed to the selective TTR-binding or fibril formation inhibition activity, the compounds identified herein are promising lead candidates for the development of ATTRv amyloidosis therapeutics.

PubMed: 39761163
DOI: 10.1021/acs.jmedchem.4c02221

実験手法

X-RAY DIFFRACTION (1.3 Å)