Lysyl oxidase-like 3 (LOXL3) (LOXL3)

Lysyl oxidase-like 3 (LOXL3) is a copper-dependent amine oxidase and a member of the lysyl oxidase (LOX) family, primarily responsible for the post-translational oxidative deamination of lysine residues in collagen and elastin [1, 8]. This enzymatic activity is essential for the formation of covalent cross-links that maintain the structural integrity and mechanical properties of the extracellular matrix (ECM) [2, 8]. Beyond its role in ECM remodeling, LOXL3 has been implicated in intracellular processes, including the regulation of the transcription factor STAT3 and the induction of epithelial-mesenchymal transition (EMT) through interactions with SNAIL [1, 4]. In clinical contexts, LOXL3 is frequently upregulated in various malignancies—such as melanoma, pancreatic cancer, and glioblastoma—where it promotes tumor invasion, metastasis, and genomic stability, often serving as a biomarker for poor prognosis [4, 5, 18]. It also plays a critical role in fibrotic diseases of the lung, liver, and heart by contributing to excessive tissue stiffening [1, 10, 17]. Therapeutic strategies targeting LOXL3 include the development of dual LOXL2/3 inhibitors (e.g., PXS-5153A) and pan-LOX inhibitors (e.g., PXS-5505), which aim to disrupt pathological ECM remodeling and sensitize tumors to other treatments [10, 11, 12]. However, therapeutic intervention must account for potential safety concerns, as loss-of-function mutations in LOXL3 are associated with Stickler syndrome, a connective tissue disorder characterized by craniofacial, ocular, and auditory defects [1, 16].

Other names

LOXLLysyl oxidase-like protein 3MYP28

Irreversible inhibition of the amine oxidase activity by targeting the lysine tyrosylquinone (LTQ) cofactor, thereby preventing the oxidative deamination of lysine residues and the subsequent formation of covalent cross-links in the extracellular matrix [10, 11].