ArticleTherapeutic advances in chronic disease2020
GNS561 acts as a potent anti-fibrotic and pro-fibrolytic agent in liver fibrosis through TGF-β1 inhibition.
Article in Therapeutic advances in chronic disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Molecular Mechanism of POSTN Mediating M2 Polarization of Kupffer Cells to Promote Hepatic Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Multi-Scale Spatial Heterogeneity of Liver Fibrosis Evaluated by MR Elastography in Rat Models.Journal of magnetic resonance imaging : JMRI · 2025Article
- PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Liver Fibrosis Resolution: From Molecular Mechanisms to Therapeutic Opportunities.International journal of molecular sciences · 2023Review
- First-In-Human Effects of PPT1 Inhibition Using the Oral Treatment with GNS561/Ezurpimtrostat in Patients with Primary and Secondary Liver Cancers.Liver cancer · 2022Article
- GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinomaAutophagy · 2022Article
- GNS561 Exhibits Potent Antiviral Activity against SARS-CoV-2 through Autophagy Inhibition.Viruses · 2022Article
- Article
- Systems Pharmacology Study of the Anti-Liver Injury Mechanism of Citri Reticulatae Pericarpium.Frontiers in pharmacology · 2021Article
- The role of autophagy in hepatic fibrosis.American journal of translational research · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatic fibrosis is the result of chronic liver injury that can progress to cirrhosis and lead to liver failure. Nevertheless, there are no anti-fibrotic drugs licensed for human use. Here, we investigated the anti-fibrotic activity of GNS561, a new lysosomotropic molecule with high liver tropism.
methodsThe anti-fibrotic effect of GNS561 was determined
resultsGNS561 significantly decreased cell viability and promoted apoptosis. Disrupting the lysosomal pH gradient impaired its pharmacological effects, suggesting that GNS561 lysosomotropism mediated cell death. GNS561 impaired cathepsin activity, leading to defective TGF-β1 maturation and autophagic processes. Moreover, GNS561 decreased HSC activation and extracellular matrix deposition by downregulating TGF-β1/Smad and mitogen-activated proteine kinase signaling and inducing fibrolysis. Finally, oral administration of GNS561 (15 mg/kg per day) was well tolerated and attenuated diethylnitrosamine-induced liver fibrosis in this rat model (decrease of collagen deposition and of pro-fibrotic markers and increase of fibrolysis).
conclusionGNS561 is a new potent lysosomotropic compound that could represent a valid medicinal option for hepatic fibrosis treatment through both its anti-fibrotic and its pro-fibrolytic effects. In addition, this study provides a rationale for targeting lysosomes as a promising therapeutic strategy in liver fibrosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.