ArticleJCI insight2019
High-throughput screening discovers antifibrotic properties of haloperidol by hindering myofibroblast activation.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Fluorinated covalent organic framework hydrogel reprograms Piezo1/YAP mechanotransduction for sustained prevention of peritendinous adhesion.Bioactive materials · 2027Article
- New approach methodologies: drug screening platform to identify antifibrotic compounds.Nature protocols · 2026Review
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- In Situ Assembly of Fluorogenic RNA for Screening Natural Anti-Liver Fibrosis Products via Dynamic Visualization of COL1A1 mRNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Endothelial-to-mesenchymal transition enhances permissiveness to AAV vectors in cardiac endothelial cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Adiponectin suppresses stiffness-dependent, profibrotic activation of lung fibroblasts.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- The Sigma-1 Receptor Exacerbates Cardiac Dysfunction Induced by Obstructive Nephropathy: A Role for Sexual Dimorphism.Biomedicines · 2024Article
- EMID2 is a novel biotherapeutic for aggressive cancers identified by in vivo screening.Journal of experimental & clinical cancer research : CR · 2024Article
- Flt1 produced by lung endothelial cells impairs ATII cell transdifferentiation and repair in pulmonary fibrosis.Cell death & disease · 2023Article
- Injectable, Drug-Eluting Nanocrystals Prevent Fibrosis and Stricture Formation In Vivo.Gastroenterology · 2023Article
- Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models.BMB reports · 2023Review
- Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.International journal of molecular sciences · 2023Review
- Impaired non-canonical transforming growth factor-β signalling prevents profibrotic phenotypes in cultured peptidylarginine deiminase 4-deficient murine cardiac fibroblasts.Journal of cellular and molecular medicine · 2021Article
- Identification of hepatic fibrosis inhibitors through morphometry analysis of a hepatic multicellular spheroids model.Scientific reports · 2021Article
- Spontaneous Lung Fibrosis Resolution Reveals Novel Antifibrotic Regulators.American journal of respiratory cell and molecular biology · 2021Article
- Review
- Molecular Dissection of Pro-Fibrotic IL11 Signaling in Cardiac and Pulmonary Fibroblasts.Frontiers in molecular biosciences · 2021Article
- Human pluripotent stem cell-derived cardiac stromal cells and their applications in regenerative medicine.Stem cell research · 2020Review
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibrosis is a hallmark in the pathogenesis of various diseases, with very limited therapeutic solutions. A key event in the fibrotic process is the expression of contractile proteins, including α-smooth muscle actin (αSMA) by fibroblasts, which become myofibroblasts. Here, we report the results of a high-throughput screening of a library of approved drugs that led to the discovery of haloperidol, a common antipsychotic drug, as a potent inhibitor of myofibroblast activation. We show that haloperidol exerts its antifibrotic effect on primary murine and human fibroblasts by binding to sigma receptor 1, independent from the canonical transforming growth factor-β signaling pathway. Its mechanism of action involves the modulation of intracellular calcium, with moderate induction of endoplasmic reticulum stress response, which in turn abrogates Notch1 signaling and the consequent expression of its targets, including αSMA. Importantly, haloperidol also reduced the fibrotic burden in 3 different animal models of lung, cardiac, and tumor-associated fibrosis, thus supporting the repurposing of this drug for the treatment of fibrotic conditions.
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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.