Transthyretin (TTR)

Eplontersen sodium is a triantennary N-acetyl galactosamine (GalNAc3-7a)-conjugated antisense oligonucleotide that targets transthyretin (TTR) mRNA, effectively inhibiting the production of both variant and wild-type TTR protein. By reducing TTR levels, Eplontersen sodium plays a crucial role in addressing conditions associated with amyloid TTR (ATTR) amyloidosis, where misfolded TTR leads to the formation of amyloid fibrils affecting the heart and peripheral nerves. This compound is pivotal for research in therapeutic strategies aimed at managing hereditary and wild-type forms of amyloidosis.

Inotersen is a 2'-O-methoxyethyl-modified antisense oligonucleotide targeting transthyretin (TTR) to inhibit its production. By binding to TTR mRNA, Inotersen promotes RNase H1-mediated degradation, leading to a decrease in both mutant and wild-type TTR synthesis in the liver. This reduction significantly mitigates amyloid fiber deposition, making Inotersen a valuable tool in research focused on hereditary transthyretin amyloidosis, including its related complications such as polyneuropathy and cardiomyopathy. Caution is advised, as high doses may lead to specific toxicities, including inflammation or tumor development in certain animal models.

Eplontersen is a triantennary N-acetyl galactosamine (GalNAc3-7a) conjugated antisense oligonucleotide that selectively targets transthyretin (TTR) mRNA. By inhibiting the synthesis of both variant and wild-type TTR proteins, Eplontersen plays a crucial role in disrupting the misfolding of TTR, which contributes to the formation of amyloid fibrils associated with ATTR amyloidosis. This compound is valuable for research applications focused on amyloid-related diseases and exploring therapeutic strategies for TTR-related pathologies.

WT-TTR Inhibitor 1 is a selective inhibitor of wild-type Transthyretin (WT-TTR), demonstrating 29.05% inhibition at a concentration of 100 μM. This compound is valuable for research applications focused on amyloidogenesis and associated diseases, including familial amyloid polyneuropathy. Its demonstrated inhibitory capacity makes it a potential tool for studying the effects of WT-TTR on protein misfolding and aggregation.

Dichlorophenyl-ABA is a potent inhibitor of transthyretin (TTR) amyloid fibril formation. It demonstrates the ability to significantly inhibit aggregate formation by over 80% in TTR L55P-expressing cells. This compound is valuable for research focused on amyloid-related disorders, particularly in understanding TTR's role in amyloidosis.

Transthyretin-IN-3 is a benzofuran analogue that selectively inhibits transthyretin (TTR) by binding to its thyroxine binding site. This compound effectively disrupts amyloid aggregation, demonstrating an IC50 value of 5.0±0.2 μM. By preventing the dissociation of TTR tetramers into unstable monomers, Transthyretin-IN-3 shows potential in research applications related to amyloid-related diseases.

Transthyretin-IN-4 is a bivalent inhibitor targeting transthyretin (TTR) amyloidosis with a bIC50 of 0.09 µM. This compound is instrumental in researching fatal heart failure with preserved ejection fraction (HFpEF) and associated fatal arrhythmias. Its ability to modulate TTR dynamics makes it a valuable tool for investigating the pathophysiology of TTR-related diseases.

Transthyretin-IN-2 is a transthyretin (TTR) inhibitor that effectively targets TTR amyloidosis, demonstrating an IC50 value of 1.31 μM. This compound plays a crucial role in the study of TTR-related amyloid diseases, providing valuable insights into therapeutic approaches for managing amyloidosis. Researchers may utilize Transthyretin-IN-2 for investigations into the biochemical pathways of TTR misfolding and aggregation.