ArticleJournal of cellular and molecular medicine2019
The lysyl oxidase like 2/3 enzymatic inhibitor, PXS-5153A, reduces crosslinks and ameliorates fibrosis.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 109 citations in OpenAlex.
- The senescence-stiffening loop: Extracellular matrix remodeling, hypoperfusion, and mitochondrial dysfunction drive tissue aging.Cell metabolism · 2026Review
- Dual-Metal Regulation of Cardiac Remodeling: Targeting the LOXL2-Ferroptosis Axis in Metal-Induced Cardiac Dysfunction.Cardiovascular toxicology · 2026Review
- Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- The Matrix Reloaded: The Hepatic Matrisome as a Therapeutic Opportunity to Fight Liver Fibrosis.Biomolecules · 2026Review
- Exploring Transcriptomic and MRI-Derived Parameters Correlations in NAFLD Fibrosis: Insights from a Rat Model.Digestive diseases and sciences · 2026Article
- The Extracellular Matrix in Liver Regeneration: Biological and Therapeutic Insights.Bioengineering (Basel, Switzerland) · 2026Review
- The role of extracellular matrix stiffness in regulating fibroblast behaviors and disease progression.Frontiers in immunology · 2026Review
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Covalent Inhibitor Screening for Targeting LOXL2: Studied by Virtual Screening and Experimental Validation.Recent patents on anti-cancer drug discovery · 2026Article
- The mechano-immunological barrier in fibrosis-associated lung cancer: targeting matrix stiffness and the Piezo1 axis for microenvironment normalization.Frontiers in pharmacology · 2026Review
- The "dual personality" of LOXL3: a tumor accomplice and a new hope for immunotherapy.Human cell · 2025Review
- The small molecule LOXL2 inhibitor SNT-5382 reduces cardiac fibrosis and achieves strong clinical target engagement.Scientific reports · 2025Article
- Decoding force-transmission linkages for therapeutic targeting and engineering.APL bioengineering · 2025Review
- Innovative Strategies in the Diagnosis and Treatment of Liver Cirrhosis and Associated Syndromes.Life (Basel, Switzerland) · 2025Review
- Mechanical forces in the tumor microenvironment: roles, pathways, and therapeutic approaches.Journal of translational medicine · 2025Review
- Review
- ECM remodeling in hypothyroidism-associated MAFLD: mechanisms, clinical relevance, and therapeutic targets.Frontiers in immunology · 2025Review
- Mechanism-guided drug development and treatment for liver fibrosis: a clinical perspective.Frontiers in pharmacology · 2025Review
- Targeted Therapy for Skeletal Muscle Fibrosis: Regulation of Myostatin, TGF-β, MMP, and TIMP to Maintain Extracellular Matrix Homeostasis.Biologics : targets & therapy · 2025Review
- Lysyl Oxidase as a Target to Reduce Graft Failure Post Solid Organ Transplantation, a Potential Target for Novel Treatment.Current medicinal chemistry · 2025Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibrosis is characterized by the excessive deposition of extracellular matrix and crosslinked proteins, in particular collagen and elastin, leading to tissue stiffening and disrupted organ function. Lysyl oxidases are key players during this process, as they initiate collagen crosslinking through the oxidation of the ε-amino group of lysine or hydroxylysine on collagen side-chains, which subsequently dimerize to form immature, or trimerize to form mature, collagen crosslinks. The role of LOXL2 in fibrosis and cancer is well documented, however the specific enzymatic function of LOXL2 and LOXL3 during disease is less clear. Herein, we describe the development of PXS-5153A, a novel mechanism based, fast-acting, dual LOXL2/LOXL3 inhibitor, which was used to interrogate the role of these enzymes in models of collagen crosslinking and fibrosis. PXS-5153A dose-dependently reduced LOXL2-mediated collagen oxidation and collagen crosslinking in vitro. In two liver fibrosis models, carbon tetrachloride or streptozotocin/high fat diet-induced, PXS-5153A reduced disease severity and improved liver function by diminishing collagen content and collagen crosslinks. In myocardial infarction, PXS-5153A improved cardiac output. Taken together these results demonstrate that, due to their crucial role in collagen crosslinking, inhibition of the enzymatic activities of LOXL2/LOXL3 represents an innovative therapeutic approach for the treatment of fibrosis.
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