Rational Design of Dual-Target Molecules via a Fragment-Merging Strategy: TGR5 Agonism and SSTR5 Antagonism
improved glucose tolerance and alleviated gallbladder filling at pharmacologically relevant doses. Collectively, these findings establish a proof of concept for dual TGR5/SSTR5 modulation as a promising therapeutic modality, providing a viable strategy to achieve potent metabolic efficacy with reduced risk of adverse effects.
Authors
- Yuqi Shi (ORCID: https://orcid.org/0000-0001-7211-331X)
- Xiaoyu Han
- Shimeng Guo
- Jun Sun (ORCID: https://orcid.org/0009-0004-2560-4916)
- Jialin Zhao
- Fanghui Han
- Mengya Li
- Xin Xie
- Jing Hu
- Yu Wang
- Chuhua Song
Institutions
- Tongji University (CN)
- Nanjing University of Chinese Medicine (CN)
- Chinese Academy of Sciences (CN)
- ShanghaiTech University (CN)
- Shanghai Institute of Materia Medica (CN)
- Institute for Advanced Study (DE)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2026-04-06
- DOI
- https://doi.org/10.1021/acs.jmedchem.5c03308
- Primary Topic
- Receptor Mechanisms and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Youth Innovation Promotion Association of the Chinese Academy of Sciences
- Taishan Scholar Project of Shandong Province