2018年4月3日 · TTR (transthyretin) cardiac amyloidosis is caused by dissociation of TTR into monomers, which misassemble into amyloid fibrils. TTR stabilizers act at the dimer–dimer interface to prevent dissociation.

2019年2月25日 · Human transthyretin (TTR) is a 55 kDa homotetrameric protein that transports thyroxine (T 4) and retinol-binding protein (RBP) in the serum and cerebrospinal fluid (Fig. 1a–c)....

Transthyretin (TTR) is a tetrameric transport protein highly conserved through vertebrate evolution and synthesized in the liver, choroid plexus, and retinal pigment epithelium. TTR transports the thyroid hormone thyroxine and the retinol-binding protein (RBP) bound to retinol (vitamin A).

Transthyretin (TTR) tetramer dissociation is rate limiting for aggregation and subunit exchange. Slowing of TTR tetramer dissociation via kinetic stabilizer binding slows cardiomyopathy progression. Quadruplicate subunit exchange comparisons of the ...

Drawing from clinically investigated AG10, we designed a constrained congener (14) that exhibits excellent TTR tetramer binding potency, prevents TTR aggregation in a gel-based assay, and possesses desirable pharmacokinetics in mice.

2016年2月23日 · Here we repurpose tolcapone, an FDA-approved molecule for Parkinson’s disease, as a potent TTR aggregation inhibitor. Tolcapone binds specifically to TTR in human plasma, stabilizes the native...

2001年11月5日 · TTR encodes transthyretin (TTR), a protein synthesized predominantly by the liver and secreted into plasma as a tetramer composed of four identical monomers. TTR is also synthesized in the retina and choroid plexus.

2022年5月1日 · Recently, effective disease-modifying therapies such as TTR tetramer stabilizers and TTR gene silencing therapies have been developed for ATTR amyloidosis. This study reviews the clinical phenotypes of ATTR amyloidosis, TTR features, and recent progress in promising therapies for ATTR amyloidosis.

2021年7月8日 · We hypothesize that kinetic stabilization of TTR tetramers via 14 is allosterically hindering all-trans-retinol-dependent RBP4-TTR tertiary complex formation and that the compound could present ancillary therapeutic utility for indications treated with RBP4 antagonists, such as macular degeneration.

2012年6月12日 · Herein we describe the molecular and structural basis of TTR tetramer stabilization by tafamidis. Tafamidis binds selectively and with negative cooperativity (K (d)s ~2 nM and ~200 nM) to the two normally unoccupied thyroxine-binding sites of the tetramer, and kinetically stabilizes TTR.