American Chemical Society (ACS)
Journal of Medicinal Chemistry
,  volume 68 ,  issue 6 ,  pages 6493-6506

Synthesis and Biological Evaluation of Peripheral 5HT2B Antagonists for Liver Fibrosis

Jihyeon Yoon 1, 2, 3, 4
, 
Won-il Choi 5, 6, 7, 8, 9, 10, 11, 12
, 
Won Il Choi 9, 10, 11, 12
, 
Won Hee Lee 11, 12, 13
, 
Gwi Bin Lee 3, 4
, 
Byeong Wook Choi 1, 2, 3, 4
, 
Pyeongkeun Kim 1, 2, 3, 4
, 
Yerim Heo 1, 2, 3, 4
, 
Yooun Heo 3, 4
, 
Dong Gun Kim 3, 4
, 
Hyeon Ah Kim 1, 2, 3, 4
, 
Myung Ae Bae 14, 15, 16, 17
, 
Myung-Ae Bae 16, 17
, 
Seong Soon Kim 14, 15, 16, 17
, 
Eun Young Lee 18
, 
Chang Myung Oh 2, 4, 19, 20
, 
Hyeok Jae Lee 1, 2, 3, 4
, 
Hyun Woo Kim 1, 2, 3, 4, 21, 22, 23, 24
, 
Wan Namkung 25
, 
Hail Kim 11, 12, 13
, 
Jinhee Ahn 1, 2, 3, 4, 18
1
 
DEPARTMENT OF CHEMISTRY
2
 
3
 
Department of Chemistry, Gwangju, Republic of Korea | 
4
 
5
 
DEPARTMENT OF PHYSIOLOGY
6
 
7
 
Graduate School of Medical Science and Engineering
8
 
9
 
Department of Physiology, Jeonju, Republic of Korea | 
10
 
11
 
Graduate School of Medical Science and Engineering, Daejeon, Republic of Korea | 
12
 
13
 
Biomedical Research Center, Daejeon, Republic of Korea | 
14
 
Bio & Drug Discovery Division
15
 
16
 
Bio & Drug Discovery Division, Daejeon, Republic of Korea | 
17
 
18
 
JD Bioscience Inc., TJS Knowledge Industrial Center, Suite 801, 208 Beon-gil Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea | 
19
 
Department of Biomedical Science and Engineering
20
 
Department of Biomedical Science and Engineering, Gwangju, Republic of Korea | 
21
 
Center For Quantum Information
22
 
23
 
Center for Quantum Information, Seoul, Republic of Korea | 
24
 
25
 
Publication type: Journal Article
Publication date: 2025-03-06
American Chemical Society (ACS)
scimago Q1
wos Q1
SJR: 1.801
CiteScore: 11.5
Impact factor: 6.8
ISSN: 00222623, 15204804
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 (5HT2B) stimulates the apoptosis of activated hepatic stellate cells and inhibits their proliferation while concurrently regressing hepatocyte proliferation. In this study, we present compound 19c, which demonstrates promising efficacy both in vitro and in vivo. 19c showed robust in vitro activity with an IC50 value of 1.09 nM and limited blood-brain barrier penetration. Furthermore, 19c did not significantly inhibit hERG and cytochrome P450 enzymes. 19c markedly reduced fibrotic deposition, with a decrease in fibrosis stage and area in the CCl4-induced liver fibrosis mouse model. Additionally, treatment with 19c led to downregulation of key fibrosis-related genes, including α-SMA, Timp1, Col1a1, and Col3a1. Taken together, these results suggest that 19c has the potential to be a novel antifibrotic agent.
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Yoon J. et al. Synthesis and Biological Evaluation of Peripheral 5HT2B Antagonists for Liver Fibrosis // Journal of Medicinal Chemistry. 2025. Vol. 68. No. 6. pp. 6493-6506.
GOST all authors (up to 50) Copy
Yoon J. et al. Synthesis and Biological Evaluation of Peripheral 5HT2B Antagonists for Liver Fibrosis // Journal of Medicinal Chemistry. 2025. Vol. 68. No. 6. pp. 6493-6506.
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TY - JOUR
DO - 10.1021/acs.jmedchem.4c03003
UR - https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c03003
TI - Synthesis and Biological Evaluation of Peripheral 5HT2B Antagonists for Liver Fibrosis
T2 - Journal of Medicinal Chemistry
AU - Yoon, Jihyeon
AU - Choi, Won-il
AU - Choi, Won Il
AU - Lee, Won Hee
AU - Lee, Gwi Bin
AU - Choi, Byeong Wook
AU - Kim, Pyeongkeun
AU - Heo, Yerim
AU - Heo, Yooun
AU - Kim, Dong Gun
AU - Kim, Hyeon Ah
AU - Bae, Myung Ae
AU - Bae, Myung-Ae
AU - Kim, Seong Soon
AU - Lee, Eun Young
AU - Oh, Chang Myung
AU - Lee, Hyeok Jae
AU - Kim, Hyun Woo
AU - Namkung, Wan
AU - Kim, Hail
AU - Ahn, Jinhee
PY - 2025
DA - 2025/03/06
PB - American Chemical Society (ACS)
SP - 6493-6506
IS - 6
VL - 68
SN - 0022-2623
SN - 1520-4804
ER -
BibTex |
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BibTex (up to 50 authors) Copy
@article{2025_Yoon,
author = {Jihyeon Yoon and Won-il Choi and Won Il Choi and Won Hee Lee and Gwi Bin Lee and Byeong Wook Choi and Pyeongkeun Kim and Yerim Heo and Yooun Heo and Dong Gun Kim and Hyeon Ah Kim and Myung Ae Bae and Myung-Ae Bae and Seong Soon Kim and Eun Young Lee and Chang Myung Oh and Hyeok Jae Lee and Hyun Woo Kim and Wan Namkung and Hail Kim and Jinhee Ahn and others},
title = {Synthesis and Biological Evaluation of Peripheral 5HT2B Antagonists for Liver Fibrosis},
journal = {Journal of Medicinal Chemistry},
year = {2025},
volume = {68},
publisher = {American Chemical Society (ACS)},
month = {mar},
url = {https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c03003},
number = {6},
pages = {6493--6506},
doi = {10.1021/acs.jmedchem.4c03003}
}
MLA
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MLA Copy
Yoon, Jihyeon, et al. “Synthesis and Biological Evaluation of Peripheral 5HT2B Antagonists for Liver Fibrosis.” Journal of Medicinal Chemistry, vol. 68, no. 6, Mar. 2025, pp. 6493-6506. https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c03003.