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Transthyretin (TTR) stabilizers and related ligands act on a plasma carrier of thyroxine and retinol. TTR circulates as a tetramer that binds thyroxine and, through retinol-binding protein 4 (RBP4), carries vitamin A. Dissociation of the tetramer into monomers is the rate-limiting step for misfolding into amyloid fibrils. In 2003 stabilization of the tetramer was shown to prevent this process in transthyretin amyloid disease. Tafamidis and tafamidis meglumine bind the thyroxine sites and act as kinetic stabilizers. Patisiran sodium is a small interfering RNA (siRNA) that lowers TTR synthesis. A 1120, an RBP4 ligand, was reported in 2009 to lower serum RBP4 levels in mice. Tinlarebant and STG-001 are listed as further antagonists of the same retinol carrier.
A 1120, a nonretinoid retinol-binding protein 4 (RBP4) antagonist, has a high affinity with the Ki value of 8.3 nM, which disrupts the interaction between RBP4 and its binding partner transthyretin.
Synonyms: LBS-008; BPN-14967
Tinlarebant is an orally active antagonist of retinol-binding protein 4 (RBP4). This compound is primarily utilized in research related to Stargardt disease, a genetic condition that leads to progressive vision loss. Tinlarebant's ability to inhibit RBP4 presents potential avenues for exploring therapeutic strategies aimed at mitigating the effects of this disorder.
STG-001 is a retinol binding protein 4 (RBP4) antagonist, specifically designed to inhibit RBP4 activity. By reducing the synthesis of retinal and diretinol, STG-001 effectively prevents photoreceptor degeneration. This compound is valuable for research applications focused on sexually precocious nephropathy (STGD).
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