The development of highly potent and selective small molecule correctors of Z ?1-antitrypsin misfolding

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