ZF874

ZF874 is a first-in-class, orally bioavailable small molecule pharmacological chaperone developed to treat alpha-1-antitrypsin deficiency (AATD), an inherited disorder caused by misfolding of the Z variant of alpha-1-antitrypsin (A1AT). The drug was designed to bind specifically to a stalled folding intermediate unique to the mutant Z-A1AT protein, catalytically accelerating its correct folding into the native, monomeric form and reducing polymer formation in liver cells. This mechanism aimed to increase circulating levels of functional A1AT and reduce pathological accumulation in the liver. Preclinical studies showed increased blood levels of A1AT and clearance of hepatic polymers in animal models. Clinical development was discontinued after Phase 1 due to adverse events involving elevated liver enzymes[1][3][8][9].