Tafamidis

Tafamidis is a potent kinetic stabilizer of transthyretin (TTR). Tafamidis binds selectively and with negative cooperativity (Kd values ∼2 nM and ∼200 nM) to the two normally unoccupied thyroxine-binding sites of the tetramer and kinetically stabilizes TTR. It prevents tetramer dissociation, the rate-limiting step in TTR misfolding and amyloidogenesis. Tafamadis also binds and stabilizes patient-derived amyloidogenic variants of TTR, including kinetically and thermodynamically less stable mutants. It is approved for the treatment of cardiomyopathy caused by transthyretin mediated amyloidosis in adults.