biostudies-literatureUnknown13(1)Chaudhari NDepartment of Health | National Health and Medical Research CouncilScarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly imprNature communications5555https://www.ebi.ac.uk/biostudies/studies/S-EPMC9500072biostudies-literatureTopical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis.PMC9500072Fear MWWallace GFindlay ADToshniwal PWood FMJoshi AClemons TDIyer KSStevenson AWJarolimek WChaudhari NYao YRea SDeng ZHortin NMelton PESayyar SfalseTopical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis.Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly impr2022-01-01T00:00:00Z2022 Sep2026-05-28T03:30:42.038Z2025-02-19T00:44:08.591ZS-EPMC95000723613800910.1038/s41467-022-33148-5