Lysyl oxidase family (LOX family)

The lysyl oxidase (LOX) family consists of five copper-dependent amine oxidases: LOX and lysyl oxidase-like proteins 1 through 4 (LOXL1–4). These enzymes play a critical role in the post-translational modification of the extracellular matrix (ECM) by catalyzing the oxidative deamination of lysine residues, which leads to the covalent cross-linking of collagen and elastin fibers [1, 2]. This process is essential for maintaining the structural integrity and mechanical strength of connective tissues throughout the body [1]. Beyond their role in the ECM, LOX family members are involved in intracellular signaling pathways that regulate cell proliferation, migration, and the epithelial-to-mesenchymal transition (EMT) [3]. In pathological states, the dysregulation of LOX enzymes is a major driver of tissue fibrosis and cancer progression; specifically, increased ECM stiffness promoted by LOX activity facilitates tumor metastasis and chemoresistance [4, 5]. Therapeutic strategies targeting the LOX family, including small-molecule pan-inhibitors and isoform-specific monoclonal antibodies, are currently being investigated for the treatment of myelofibrosis, NASH, and various solid tumors [6]. [1] Vallet and Ricard-Blum (2019) Essays Biochem; [2] Moon et al. (2014) Nat Rev Cancer; [3] Barker et al. (2012) Cancer Res; [4] Cox et al. (2016) Nat Rev Cancer; [5] Setargew et al. (2021) Gene; [6] Pharmaxis Ltd (2023) ClinicalTrials.gov.

Other names

Protein-lysine 6-oxidase familyLOX/LOXL familyCopper-dependent amine oxidase familyLysyl oxidase-like proteins

Irreversible inhibition of the copper-dependent oxidative deamination of lysine and hydroxylysine residues; competitive inhibition of the catalytic site; monoclonal antibody-mediated neutralization of extracellular enzyme activity.