tafamidis-amide

Tafamidis-amide (also known as compound 1a) is a brain-permeable piperazine amide prodrug of the transthyretin (TTR) kinetic stabilizer tafamidis. It was designed to enhance central nervous system bioavailability and overcome the blood-brain barrier (BBB) limitations of the parent compound. Upon crossing the BBB, tafamidis-amide undergoes physiological proteolysis to release active tafamidis, which stabilizes the TTR tetramer. TTR acts as a natural amyloid-beta (Aβ) sequestration protein, preventing its oligomerization and promoting clearance. Tafamidis-amide is being investigated for its neuroprotective potential in sporadic Alzheimer's disease (sAD) and other TTR amyloidosis-related central nervous system pathologies. Preclinical studies in mouse models have demonstrated its ability to reduce neuroinflammation, restore insulin signaling, and lower oxidative stress markers, particularly in the hippocampus.

Other names

1acompound 1acompound1acompound-1apiperazine amide derivative of tafamidistafamidis amide