ArticleCommunications biology2023
Selectivity matters: selective ROCK2 inhibitor ameliorates established liver fibrosis via targeting inflammation, fibrosis, and metabolism.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Evolving Paradigms in Chronic Graft-Versus-Host Disease: From Global Immunosuppression to Precision Targeted and Cell-Based Therapies.Stem cell reviews and reports · 2026Pooled it
- Novel highly selective ROCK2 inhibitor (TDI01) for the treatment of chronic graft-versus-host disease: a multicenter, open-label phase Ib/II study.Signal transduction and targeted therapy · 2026Trial
- Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study.Blood advances · 2025Trial
- Beyond cytoskeletal regulation: Rho-associated, coiled-coil-containing protein kinase 2 in kidney inflammation and fibrosis.Histology and histopathology · 2026Review
- Targeting RhoA/ROCK Signaling to Modulate Extracellular Matrix Remodeling in Corneal Endothelial Dystrophies.Investigative ophthalmology & visual science · 2026Article
- Alterations of actin in aging.Journal of cell science · 2026Review
- AH001: A New Drug Targeting RhoA in Heart Failure.Circulation research · 2026Article
- Discovery of selective ROCK2 inhibitors with free radical scavenging ability for the treatment of gouty arthritis.Molecular diversity · 2025Article
- Restoring brain barriers: an innovative approach for treating neurological disorders.Fluids and barriers of the CNS · 2025Review
- Macrophages in graft-versus-host disease (GVHD): dual roles as therapeutic tools and targets.Clinical and experimental medicine · 2025Review
- Mechanosignaling via Integrins: Pivotal Players in Liver Fibrosis Progression and Therapy.Cells · 2025Review
- Advancing therapeutic frontiers: a pipeline of novel drugs for luminal and perianal Crohn's disease management.Therapeutic advances in gastroenterology · 2024Review
- The role of the cytoskeleton in fibrotic diseases.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The pathogenesis of hepatic fibrosis is driven by dysregulated metabolism precipitated by chronic inflammation. Rho-associated coiled-coil-containing protein kinases (ROCKs) have been implicated in these processes, however the ability of selective ROCK2 inhibition to target simultaneously profibrotic, pro-inflammatory and metabolic pathways remains undocumented. Here we show that therapeutic administration of GV101, a selective ROCK2 inhibitor with more than 1000-fold selectivity over ROCK1, attenuates established liver fibrosis induced by thioacetamide (TAA) in combination with high-fat diet in mice. GV101 treatment significantly reduces collagen levels in liver, associated with downregulation of pCofilin, pSTAT3, pAkt, while pSTAT5 and pAMPK levels are increased in tissues of treated mice. In vitro, GV101 inhibits profibrogenic markers expression in fibroblasts, adipogenesis in primary adipocytes and TLR-induced cytokine secretion in innate immune cells via targeting of Akt-mTOR-S6K signaling axis, further uncovering the ROCK2-specific complex mechanism of action and therapeutic potential of highly selective ROCK2 inhibitors in liver fibrosis.
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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.