Lysyl oxidase and lysyl oxidase-like enzymes (LOX/LOXL)

Lysyl oxidase (LOX) and lysyl oxidase-like (LOXL1-4) enzymes are copper-dependent amine oxidases that play a critical role in the covalent cross-linking of collagen and elastin fibers within the extracellular matrix (ECM) (UniProt P06733; Vallet & Ricard-Blum, 2019). By catalyzing the oxidative deamination of lysine residues, these enzymes ensure the structural integrity and mechanical strength of connective tissues (PubMed PMC6471163). Pathologically, the overexpression of LOX/LOXL enzymes is strongly associated with the progression of organ fibrosis and the promotion of tumor metastasis through ECM stiffening and signaling pathways like TGF-beta (Barker et al., 2012; Cox et al., 2016). Therapeutic strategies targeting this family include small molecule inhibitors like PXS-5505 and monoclonal antibodies like Simtuzumab, which aim to halt fibrotic progression and disrupt the pre-metastatic niche (ClinicalTrials.gov NCT04676529; Setargew et al., 2021). Despite their therapeutic potential, targeting these enzymes carries risks of systemic toxicity, including osteolathyrism and vascular defects, due to their fundamental role in maintaining normal tissue architecture (Rodriguez et al., 2008).

Other names

Protein-lysine 6-oxidaseLOX familyLysyl oxidase-like proteinCopper-dependent amine oxidaseLOXL1LOXL2LOXL3LOXL4

Inhibition of the oxidative deamination of lysine and hydroxylysine residues in collagen and elastin precursors, which prevents the formation of covalent cross-links and reduces extracellular matrix stiffness.