PXS-4787 is a potent and selective inhibitor of lysyl oxidase (LOX) with broad-spectrum activity. It effectively suppresses lysyl oxidase activity by acting on its mechanisms. The compound displays inhibitory effects with IC50 values of 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 [1].

Lysyl oxidases stabilize collagen which is the main component of scar tissue, and drive scar stiffness and appearance [1]. PXS-4787 (0-10 μM; 15 min-4 h) dose- and time-dependently inhibits lysyl oxidase and displays comparable inhibitory activity across species [1]. PXS-4787 (0-100 μM; 72 h) is well tolerated by primary human dermal fibroblasts, (10 μM; 11 d) reduces collagen formation, deposition and crosslinking in primary human dermal fibroblasts cultured in vitro [1]. PXS-4787 (10 μM; 48 h) induces differential gene expression in fibroblasts and keratinocytes, including COL1A1, LOX, GAPDH, PGK1 [1]. Immunofluorescence [1] Cell Line: Primary human dermal fibroblasts cultured in vitro Concentration: 0, 1, 10 μM Incubation Time: 11 days Result: Significantly reduced in the 10 μM treatment group. RT-PCR [1] Cell Line: Cultured fibroblasts and keratinocytes (isolated from five different patients) Concentration: 10 μM Incubation Time: 48 hours Result: Resulted four genes with significant differential expression in fibroblasts and two differentially expressed genes in keratinocytes.

PXS-4787 (3%, oil in water cream; external application; once daily, for 28 days) lowers collagen deposition and cross-linkin in murine models of injury and fibrosis under topical application [1]. PXS-4787 (3%, oil in water cream; external application; once daily, for 12 weeks) also significantly improves scar appearance without reducing tissue strength in porcine injury models under topical application [1]. Animal Model: Porcine excision injury model (female Juvenile pigs, 18-20 kg) [1] Dosage: 3%, oil in water cream; 400 mg cream applied to 16 cm 2 Administration: External application; 1, 2 and 3 weeks post-injury; once dailly, for 12 weeks Result: Improved the appearance of scar in relevant in vivo models, indicative of a targetdriven, as opposed to compound-specific, effect.