Tafamidis meglumine (Fx-1006A) is a potent and selective transthyretin (TTR) stabilizer, shows comparable potency and efficacy to the mutumant homotetramers V30M-TTR, V122I-TTR and wild type WT-TTR, with EC 50 s of 2.7-3.2 μM. Tafamidis meglumine inhibits amyloidogenesis
In Vitro
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. Tafamidis (0-7.2 μM) dose-dependently inhibits WT-TTR amyloidogenesis after treatment for 72 hours at a pH of 4.4-4.5. MCE has not independently confirmed the accuracy of these methods. They are for reference only.