Shang Li, Xinxin Li, Liangliang Ma, Zhongwen Luo, Fucheng Yin, Yonglei Zhang, Yifan Chen, Siyuan Wan, Han Zhou, Xiaobing Wang,* Lingyi Kong*, Polypharmacological Drug Design Guided by Integrating Phenotypic and Restricted Fragment Docking Strategies,  Journal of Medicinal Chemistry, 2024, 67, 18, xxx, DOI: 10.1021/acs.jmedchem.4c01731.

This cover depicts a promising approach in drug discovery for the treatment of Alzheimer’s disease. Via phenotypic discovery of triple-target combinations with synergistic effects on microglia, an in silico restricted fragment docking strategy was developed to achieve “three birds with one stone”. The optimal ligand showed in vitro and in vivo efficacy by precisely modulating targets of interest.