GS-607601
/ Gilead
- LARVOL DELTA
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December 12, 2025
A novel cell-permeable LOXL2 inhibitor PAT-1251 potently suppresses biliary liver fibrosis via collagen crosslinking-dependent and -independent mechanisms.
(PubMed, Hepatol Commun)
- "While having comparable extracellular effects on collagen crosslinking in vivo, the cell-permeable LOXL2 inhibitor PAT-1251 exerted potent antifibrotic activity in hepatic progenitors and HSC cultures compared with the anti-LOXL2 antibody. PAT-1251 substantially outperformed the anti-LOXL2 antibody in the BALB/c. Mdr2-/- model of biliary fibrosis, suggesting that intracellular LOXL2 targeting is therapeutically important in addition to its well-characterized extracellular collagen crosslinking activity."
Journal • Cardiovascular • Fibrosis • Hepatology • Hypertension • Immunology • Liver Cirrhosis • Portal Hypertension • Primary Biliary Cholangitis • ABCB4
August 23, 2024
Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2.
(PubMed, Cell Rep Med)
- "Thus, AB0023 is anti-angiogenic but does not inhibit LOXL2 catalytic activity, collagen cross-linking, or tissue stiffening. These findings have implications for the interpretation of the lack of efficacy of simtuzumab in clinical trials of fibrotic diseases."
Journal • Fibrosis • Immunology
June 13, 2023
SPECT Imaging of Lysyl Oxidase-like 2 in a Model of Idiopathic Pulmonary Fibrosis.
(PubMed, Mol Pharm)
- "The bifunctional chelator DOTAGA-PEG-NH was chemoenzymatically conjugated to the murine antibody AB0023 using microbial transglutaminase, resulting in a degree of labeling (number of chelators per antibody) of 2.3. In conclusion, we report the first radioimmunotracer targeting the protein LOXL2 for nuclear imaging of IPF. The tracer showed promising results in a preclinical model of bleomycin-induced pulmonary fibrosis, with high lung uptake in fibrotic areas, and accounted for the antifibrotic activity of nintedanib."
Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases
September 29, 2022
Inhibition of lysyl oxidase‑like 2 ameliorates folic acid‑induced renal tubulointerstitial fibrosis.
(PubMed, Exp Ther Med)
- "The present study evaluated the effect of LOXL2 inhibition using an inhibitory monoclonal antibody (AB0023) on tubulointerstitial fibrosis in a folic acid-induced tubulointerstitial fibrosis mouse model. Following transforming growth factor-β (TGF-β) challenge, LOXL2-deficient HK-2 cells exhibited significantly lower expression of the mesenchymal markers vimentin and fibronectin than control HK-2 cells. In conclusion, LOXL2 inhibition ameliorates renal fibrosis through the TGF-β/Smad signalling pathway."
Journal • Fibrosis • Immunology • Oncology • FN1 • SMAD4 • TGFB1 • VIM
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