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Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis


Chaudhari, N and Findlay, AD and Stevenson, AW and Clemons, TD and Yao, Y and Joshi, A and Sayyar, S and Wallace, G and Rea, S and Toshniwal, P and Deng, Z and Melton, PE and Hortin, N and Iyer, KS and Jarolimek, W and Wood, FM and Fear, MW, Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis, Nature Communications, 13, (1) pp. 1-14. ISSN 2041-1723 (2022) [Refereed Article]

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DOI: doi:10.1038/s41467-022-33148-5


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 improves scar appearance without reducing tissue strength in porcine injury models. PXS-6302 therefore represents a promising therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases.

Item Details

Item Type:Refereed Article
Keywords:scars, wound healing, DNA methylation, RNA-Seq, fibrosis
Research Division:Biological Sciences
Research Group:Bioinformatics and computational biology
Research Field:Genomics and transcriptomics
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Melton, PE (Dr Phillip Melton)
ID Code:155442
Year Published:2022
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2023-02-20
Last Modified:2023-02-21

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