The Development Of Highly Potent And Selective Small Molecule Correctors Of Z Alpha 1-Antitrypsin Misfolding

?1-antitrypsin deficiency is characterised by the misfolding and intracellular polymerisation of mutant ?1antitrypsin protein within the endoplasmic reticulum (ER) of hepatocytes. Small molecules that bind and stabilise Z ?1-antitrypsin were identified via a DNA-encoded library screen. A subsequent structure based optimisation led to a series of highly potent, selective and cellular active ?1-antitrypsin correctors.