PXS-4159

PXS-4159 is an orally active, small molecule dual inhibitor of lysyl oxidase-like 2 (LOXL2) and lysyl oxidase-like 3 (LOXL3), developed by Pharmaxis (now Syntara). The lysyl oxidase family of enzymes is responsible for the oxidative deamination of lysine residues in collagen and elastin, a critical step in the cross-linking of the extracellular matrix (ECM). In pathological fibrotic conditions, overactivity of LOXL2 and LOXL3 leads to excessive ECM deposition and tissue stiffening. PXS-4159 acts as a mechanism-based, irreversible inhibitor that binds covalently to the active site of these enzymes, thereby halting the progression of fibrosis. While initially investigated for indications such as idiopathic pulmonary fibrosis (IPF) and non-alcoholic steatohepatitis (NASH), the development of PXS-4159 appears to have been superseded by other candidates in the Pharmaxis pipeline, such as PXS-5153 and the pan-LOX inhibitor PXS-5505.