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Article Abstract
Liver fibrosis is characterized by an excessive accumulation of extracellular matrix components, leading to the distortion of liver architecture and function. Recent studies have shown that antagonizing 5-hydroxytryptamine receptor 2B (5HT) stimulates the apoptosis of activated hepatic stellate cells and inhibits their proliferation while concurrently regressing hepatocyte proliferation. In this study, we present compound , which demonstrates promising efficacy both and . showed robust activity with an IC value of 1.09 nM and limited blood-brain barrier penetration. Furthermore, did not significantly inhibit hERG and cytochrome P450 enzymes. markedly reduced fibrotic deposition, with a decrease in fibrosis stage and area in the CCl-induced liver fibrosis mouse model. Additionally, treatment with led to downregulation of key fibrosis-related genes, including α-SMA, Timp1, Col1a1, and Col3a1. Taken together, these results suggest that has the potential to be a novel antifibrotic agent.
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| http://dx.doi.org/10.1021/acs.jmedchem.4c03003 | DOI Listing |
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