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Updated: Apr 21, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Development of second-generation small-molecule RhoA inhibitors with enhanced water solubility, tissue potency, and
Sheng Ma1, Jing Deng, Baoli Li
1Department of Clinical Pharmacology Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shi Zhi Street, Suzhou 215006 (China).
Abstract:
RhoA, a member of the Rho GTPases, is involved in a variety of cellular functions and could be a suitable therapeutic target for the treatment of cardiovascular diseases. However, few small-molecule RhoA inhibitors have been reported. Based on our previously reported lead compounds, 32 new 2-substituted quinoline (or quinoxaline) derivatives were synthesized and tested in biological assays. Six compounds showed high RhoA inhibitory activities, with IC50 values of 1.17-1.84 μM. Among these, (E)-3-(3-(ethyl(quinolin-2-yl)amino)phenyl)acrylic acid (26 b) and (E)-3-(3-(butyl(quinolin-2-yl)amino)phenyl)acrylic acid (26 d) demonstrated noticeable vasorelaxation effects against phenylephrine-induced contraction in thoracic aorta artery rings, and compound 26 b had good water solubility and showed significant in vivo efficacy, which was similar to that of 5-(1,4-diazepane-1-sulfonyl)isoquinoline (fasudil) in a subarachnoid hemorrhage-cardiovascular model. To the best of our knowledge, compound 26 b is the first example of a small- molecule RhoA inhibitor with potent in vivo efficacy, which could serve as a good lead for designing cardiovascular agents.
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