A substructure combination strategy to create potent and selective transthyretin kinetic stabilizers that prevent amyloidogenesis and cytotoxicity.


Transthyretin aggregation-associated proteotoxicity appears to cause several human amyloid diseases. Rate-limiting tetramer dissociation and monomer misfolding of transthyretin (TTR) occur before its aggregation into cross-beta-sheet amyloid fibrils. Small molecule binding to and preferential stabilization of the tetrameric state of TTR over the… (More)
DOI: 10.1021/ja908562q


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