Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (Lysyl hydroxylase) (PLOD (LH))

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD), also known as lysyl hydroxylase (LH), is a family of three enzymes (PLOD1, PLOD2, and PLOD3) essential for the post-translational modification of collagen. These enzymes catalyze the hydroxylation of specific lysine residues in procollagen, a prerequisite for the formation of stable covalent cross-links that provide structural integrity to the extracellular matrix (ECM). While PLOD1 is critical for normal connective tissue development, PLOD2 and PLOD3 are frequently upregulated in various cancers and fibrotic conditions. In the tumor microenvironment, PLOD-mediated collagen remodeling creates a stiffened matrix that facilitates cancer cell migration and metastasis. Consequently, PLOD/LH has emerged as a promising therapeutic target for anti-metastatic and anti-fibrotic treatments. Current drug discovery efforts focus on small-molecule inhibitors like minoxidil and novel 2-oxoglutarate analogs, although achieving isoform specificity and avoiding systemic connective tissue side effects remain significant challenges.

Other names

Lysyl hydroxylaseLHProcollagen-lysine 5-dioxygenaseLH1LH2LH3PLOD1PLOD2PLOD3

Inhibition of lysyl hydroxylase enzymatic activity to prevent the formation of stable collagen cross-links, thereby reducing extracellular matrix stiffness and inhibiting tumor cell migration or fibrotic progression.