ArticleInternational journal of molecular sciences2022
Pan-Lysyl Oxidase Inhibitor PXS-5505 Ameliorates Multiple-Organ Fibrosis by Inhibiting Collagen Crosslinks in Rodent Models of Systemic Sclerosis.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- A phase I/IIa trial of PXS-5505, a novel pan-lysyl oxidase inhibitor, in advanced myelofibrosis.Haematologica · 2025Trial
- Biofabrication and artificial intelligence strategies for investigating solid- and fluid-pressure mechanobiology in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2026Review
- The inflammatory/fibrotic axis across organs: myelofibrosis as a model of reversibility.JCI insight · 2026Review
- LOX Inhibition Disrupts a Collagen-Integrin-MYC Axis to Suppress Progression of Invasive Lobular Carcinoma.Cancer research · 2026Article
- Reprogrammed Fibrotic Niche Fuels Lung Cancer Initiation and Reciprocal Remodeling.International journal of biological sciences · 2026Review
- Around the collagen triple helix: an introduction to studying associated genetic and acquired diseases.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Targeting Dermal Fibroblast Senescence: From Cellular Plasticity to Anti-Aging Therapies.Biomedicines · 2025Review
- Nanoscale structural alteration of lung collagen in response to strain and bleomycin injury.Scientific reports · 2025Article
- Targeting vascular adhesion protein-1 and myeloperoxidase with a dual inhibitor SNT-8370 in preclinical models of inflammatory disease.Nature communications · 2025Article
- Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis.Nature communications · 2025Article
- Spiny mice (Acomys) have evolved cellular features to support regenerative healing.Annals of the New York Academy of Sciences · 2025Review
- Tension-induced organelle stress: an emerging target in fibrosis.Trends in pharmacological sciences · 2025Review
- The Function of the TGFβ Signaling Pathway in Connective Tissue Diseases: From Biology to Clinical Application.Journal of inflammation research · 2025Review
- Lysyl Oxidase as a Target to Reduce Graft Failure Post Solid Organ Transplantation, a Potential Target for Novel Treatment.Current medicinal chemistry · 2025Review
- Mechanism-guided drug development and treatment for liver fibrosis: a clinical perspective.Frontiers in pharmacology · 2025Review
- Burn scar pain: from mechanisms to treatments.Frontiers in physiology · 2025Review
- Identification of Novel Biomarkers and Potential Therapeutic Targets for Systemic Sclerosis: An Integrated Analysis of Plasma Proteome-Wide Mendelian Randomization and Transcriptome.Journal of inflammation research · 2025Article
- Rapid LC-MS/MS Evaluation of Collagen and Elastin Crosslinks in Human and Mouse Lung Tissue with a Novel Bioanalytical Surrogate Matrix Approach.International journal of molecular sciences · 2024Article
- Pan-lysyl oxidase inhibition disrupts fibroinflammatory tumor stroma, rendering cholangiocarcinoma susceptible to chemotherapy.Hepatology communications · 2024Article
- Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 α-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.
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