Discovery of Potent and Selective Pyridone-Based Small Molecule Kinetic Stabilizers of Amyloidogenic Immunoglobulin Light Chains

Kinetic stabilization of amyloidogenic immunoglobulin light chains (LCs) through small molecule binding may become the first treatment for the proteinopathy component of light chain amyloidosis (AL). Kinetic stabilizers selectively bind to the native state over the misfolding transition state, slowing denaturation. Prior λ full-length LC dimer (FL LC