Landmark Liver Fibrosis Research Published in Cell, Cloud-Clone Aids ROCK2-Targeted Drug TDI01 Development
Breakthrough Study in Cell Paves Way for ROCK2-Targeted Therapy TDI01 in Liver Fibrosis
KATY, TX / 500NewsWire / June 16, 2026 / In April 2026, a groundbreaking study—Selective targeting of endothelial and perivascular angiocrine ROCK2 treats liver fibrosis—was published online in the prestigious international journal Cell. This research reveals for the first time that selective upregulation of ROCK2 in liver endothelial cells and perivascular hepatic stellate cells serves as a core mechanism driving the progression of liver fibrosis. The study has successfully led to the development of a highly selective ROCK2 inhibitor, TDI01. Preliminary clinical data confirm that this drug can significantly reverse liver fibrosis and improve liver function, offering a novel solution to a field that has long lacked effective targeted therapies.
Urgent Clinical Need for Liver Fibrosis, Long-Standing Gap in Targeted Treatment
Liver fibrosis is a key pathological process in chronic liver diseases such as metabolic dysfunction-associated steatohepatitis (MASH). Its core mechanism involves the abnormal activation and differentiation of hepatic stellate cells (HSCs) into myofibroblasts, leading to excessive collagen secretion and disruption of liver structure. This disease can progressively develop into cirrhosis or even liver cancer. However, current clinical treatment options are limited, lacking clearly defined mechanism-based targeted therapies, presenting a significant unmet clinical need.
Mechanistic Breakthrough: ROCK2 Emerges as a Precision Therapeutic Target
Utilizing RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analyses, the research team discovered that Rho-associated coiled-coil containing kinase 2 (ROCK2) is specifically highly expressed in endothelial cells (ECs) and perivascular HSCs of human fibrotic livers. Furthermore, its protein levels increase progressively with fibrosis staging (F0-F4). In contrast, its homolog ROCK1 showed no significant differential expression and is widely distributed across various cell types. These results clearly identify ROCK2 as a potential target for precision treatment of liver fibrosis. The team further validated this using ROCK2-knockout mice (ROCK2^△EC/△EC^) in carbon tetrachloride (CCl4)-induced liver fibrosis and MASH models. Compared to control mice, the knockout models exhibited significantly reduced liver fibrosis severity, as well as lower levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), confirming endothelial cell ROCK2 as a key driver of fibrosis.
Breakthrough Drug: TDI01 Achieves Safe and Effective Reversal of Liver Fibrosis
Based on the crystal structure of ROCK2, researchers designed and synthesized 686 compounds. Through screening for ROCK2-selective inhibitory activity, pharmacokinetic (PK) analysis, and toxicology testing, TDI01 was ultimately selected as the core drug candidate. Cryo-electron microscopy structural analysis reveals that TDI01 binds to a hydrophobic pocket of ROCK2 (partially overlapping with the ATP-binding pocket), inducing ROCK2 to form an inactive “DFG-out” conformation, with the L210 residue being a critical site for achieving highly selective binding.
Preclinical studies demonstrated that in multiple liver fibrosis models, including mice and minipigs, oral administration of TDI01 effectively reduced liver stiffness, decreased collagen deposition, reversed liver sinusoidal endothelial cell (LSEC) capillarization, alleviated inflammation and steatosis, comprehensively restoring liver structure and function.
Preliminary clinical study results are highly encouraging: Among 62 healthy volunteers who received TDI01, no severe adverse events were reported, with excellent pharmacokinetic properties and a good safety profile. In a study involving 6 liver fibrosis patients treated with 200 mg once daily for 24 weeks, 5 patients showed sustained reductions in liver stiffness and significant improvements in key fibrosis biomarkers. Liver function tests tended to normalize, and liver biopsies revealed reduced collagen deposition. Notably, even patients with stage F4 cirrhosis exhibited histological improvement. The drug specifically inhibits ROCK2 activity without affecting ROCK1, demonstrating excellent target selectivity.
Robust Support: Key Data from Premier Journal Study Provides Critical Backing
It is noteworthy that in this high-impact Cell study, the MCP1/CCL2 ELISA Kit supplied critical data for mechanistic validation and efficacy assessment. It accurately measured chemokine CCL2 levels, providing direct evidence for the pro-inflammatory and pro-fibrotic effects of galectin-3, as well as the anti-fibrotic efficacy of TDI01.
Backed by an SPF-grade experimental animal center and a proprietary R&D resource library, a comprehensive suite of research tools for humans, rats, mice, and other species has been established. The product portfolio encompasses full-chain solutions, including proteins, antibodies, ELISA kits, primary cells, and animal models. Certified with ISO9001, ISO13485, and ISO4001 quality management systems, in-house R&D and production ensure product stability and consistency. As of the end of 2025, products have contributed to the publication of over 42,000 SCI-indexed papers, with hundreds of these findings appearing in top-tier international journals like Nature, Science, and Cell, establishing the brand as a trusted partner for global researchers.
This significant breakthrough in ROCK2-targeted therapy for liver fibrosis not only addresses a long-standing gap in treatment options but also brings new hope for reversing chronic liver disease. It further underscores the core value of high-quality research tools in top-tier life science research.
Article Link:
Hu Y, Yang B, Ding BS. Selective targeting of endothelial and perivascular angiocrine ROCK2 treats liver fibrosis. Cell. 2026 Mar 6(26)00166-2. doi: 10.1016/j.cell.2026.02.001. Epub ahead of print. PMID: 41794026.
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