{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:25:33Z","timestamp":1790227533267,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pharmaxis Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic sclerosis (SSc) is characterised by progressive multiple organ fibrosis leading to morbidity and mortality. Lysyl oxidases play a vital role in the cross-linking of collagens and subsequent build-up of fibrosis in the extracellular matrix. As such, their inhibition provides a novel treatment paradigm for SSc. A novel small molecule pan-lysyl oxidase inhibitor, PXS-5505, currently in clinical development for myelofibrosis treatment was evaluated using in vivo rodent models resembling the fibrotic conditions in SSc. Both lysyl oxidase and lysyl oxidase-like 2 (LOXL2) expression were elevated in the skin and lung of SSc patients. The oral application of PXS-5505 inhibited lysyl oxidase activity in the skin and LOXL2 activity in the lung. PXS-5505 exhibited anti-fibrotic effects in the SSc skin mouse model, reducing dermal thickness and \u03b1-smooth muscle actin. Similarly, in the bleomycin-induced mouse lung model, PXS-5505 reduced pulmonary fibrosis toward normal levels, mediated by its ability to normalise collagen\/elastin crosslink formation. PXS-5505 also reduced fibrotic extent in models of the ischaemia-reperfusion heart, the unilateral ureteral obstruction kidney, and the CCl4-induced fibrotic liver. PXS-5505 consistently demonstrates potent anti-fibrotic efficacy in multiple models of organ fibrosis relevant to the pathogenesis of SSc, suggesting that it may be efficacious as a novel approach for treating SSc.<\/jats:p>","DOI":"10.3390\/ijms23105533","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T13:06:23Z","timestamp":1652706383000},"page":"5533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Pan-Lysyl Oxidase Inhibitor PXS-5505 Ameliorates Multiple-Organ Fibrosis by Inhibiting Collagen Crosslinks in Rodent Models of Systemic Sclerosis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6652-6214","authenticated-orcid":false,"given":"Yimin","family":"Yao","sequence":"first","affiliation":[{"name":"Drug Discovery, Pharmaxis Ltd., Sydney, NSW 2086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Findlay","sequence":"additional","affiliation":[{"name":"Drug Discovery, Pharmaxis Ltd., Sydney, NSW 2086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Stolp","sequence":"additional","affiliation":[{"name":"Drug Discovery, Pharmaxis Ltd., Sydney, NSW 2086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Rayner","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Kensington, Sydney, NSW 2031, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjetil","family":"Ask","sequence":"additional","affiliation":[{"name":"Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Jarolimek","sequence":"additional","affiliation":[{"name":"Drug Discovery, Pharmaxis Ltd., Sydney, NSW 2086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1517\/21678707.2016.1114454","article-title":"Treatment of Rapidly Progressive Systemic Sclerosis: Current and Futures Perspectives","volume":"4","author":"Mendoza","year":"2016","journal-title":"Expert Opin. 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