PXS-4787 is a Specific Pan-LOX (Lysyl Oxidase) Inhibitor

LOX (lysyl oxidase) is encoded in the human body by the LOX gene. This gene is located on human chromosome 5 and encodes a polypeptide of 417 amino acids. The first 21 of these residues constitute the signal peptide, while the carboxyl terminus contains reactive copper ions, lysine, tyrosine and cysteine residues. Together, they constitute the catalytic active site. LOX is a quinone-like copper amine oxidase with a reaction highly dependent on the cofactor lysyl tyrosyl quinone (LTQ). That can catalyze the conversion of lysine residues to highly reactive aldehydes. These aldehydes further undergo spontaneous chemical reactions with other LOX-derived aldehyde residues or unmodified lysine residues, initiating the formation of covalent cross-links in elastin and collagen. Its inhibition then causes osteomalacia, at the same time, its upregulation by tumor cells may promote the metastasis of existing tumors to malignant carcinomas.

PXS-4787 is a specific pan-LOX inhibitor.

From: Wei S, et al. Exp Ther Med. 2020 Jul;20(1):163-172.

PXS-4787 is a specific and potent lysyl oxidase inhibitor, which can eliminate lysyl oxidase activity. The IC50s for LOX inhibition by PXS-4787 are 2 μM (bovine LOX), 3.2 μM (rh LOXL1), 0.6 μM (rh LOXL2), 1.4 μM (rh LOXL3), and 0.2 μM (rh LOXL4), respectively. Meanwhile, PXS-4787 (0-10 μM; 15 min-4 h) inhibits LOX dose- and time-dependently, and exhibits comparable inhibitory activity across species. PXS-4787 (0-100 μM; 72 h) is well tolerated by primary human dermal fibroblasts. Besides, it (10 μM; 11 d) significantly reduces collagen formation, deposition, and cross-linking in primary human dermal fibroblasts cultured in vitro. Furthermore, PXS-4787 (10 μM; 48 h) induces differential gene expression in fibroblasts and keratinocytes, including COL1A1, LOX, GAPDH, and PGK1.

It also has good results in vivo experiments. PXS-4787 (3%, oil in water cream) can reduce collagen deposition and cross-linking in murine models of injury and fibrosis under topical application by external application once a day for 28 days. Moreover, PXS-4787 (3%, oil in water cream, 400 mg cream applied to 16 cm2) also significantly improves scar appearance without reducing tissue strength in porcine injury models under topical application by external application once a day for 12 weeks. That suggests a target-driven effect rather than a compound-specific effect.

In conclusion, PXS-4787 is a specific and effective pan-LOX (lysyl oxidase) inhibitor, that can reduce collagen formation, deposition, and cross-linking


[1] Chaudhari N, et al. Nat Commun. 2022 Sep 22;13(1):5555. 
[2] Sylvain D Vallet, et al. Essays Biochem. 2019 Sep 13;63(3):349-364.