What binding site does tafamidis target to slow fibril formation?

• A. The unoccupied T4 binding site
• B. A hydrophobic pocket in albumin
• C. The active site of cyclooxygenase
• D. A receptor on hepatocytes

Answer: (A)

Tafamidis works by stabilizing transthyretin (TTR) through binding to its thyroxine-binding pockets. By occupying the unoccupied T4 binding sites on the TTR tetramer, tafamidis prevents the tetramer from falling apart into misfolded monomers that can aggregate into amyloid fibrils. This stabilization slows fibril formation and can slow disease progression in hereditary transthyretin amyloidosis. The other targets listed—albumin’s hydrophobic pocket, the active site of cyclooxygenase, or a hepatocyte receptor—are not involved in this mechanism, so they don’t explain how tafamidis reduces fibril formation.