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

journal contribution
posted on 2023-05-21, 16:32 authored by Chaudhari, N, Findlay, AD, Stevenson, AW, Clemons, TD, Yao, Y, Joshi, A, Sayyar, S, Wallace, G, Rea, S, Toshniwal, P, Deng, Z, Phillip MeltonPhillip Melton, Hortin, N, Iyer, KS, Jarolimek, W, Wood, FM, Fear, MW
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.

History

Publication title

Nature Communications

Volume

13

Pagination

1-14

ISSN

2041-1723

Department/School

Menzies Institute for Medical Research

Publisher

Nature Pub. Group

Place of publication

United Kingdom

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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    University Of Tasmania

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