PF-06291826(Tafamidis) — Datasheet

Biological Activity

Tafamidis(Fx1006A) is a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade.Target: OthersTafamidis is a drug for the amelioration of transthyretin-related hereditary amyloidosis.Tafamidis functions by kinetic stabilization of the correctly folded tetrameric form of the transthyretin (TTR) protein. 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. Patient-derived amyloidogenic variants of TTR, including kinetically and thermodynamically less stable mutants, are also stabilized by tafamidis binding. The crystal structure of tafamidis-bound TTR suggests that binding stabilizes the weaker dimer-dimer interface against dissociation, the rate-limiting step of amyloidogenesis [1].

Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.