(Peer-Reviewed) Discovery of novel aspartate derivatives as highly potent and selective FXIa inhibitors
Ling Zhang 章凌 ¹, Wei Chen 陈威 ², Ningning Yao 姚宁宁 ¹, Shuzeng Hou 侯书增 ¹, Zhiwei Meng 孟志伟 ¹, Yi Kong 孔毅 ², Chenzhong Liao 廖晨钟 ¹, Zhouling Xie 谢周令 ¹
¹ Department of Pharmaceutical Sciences and Engineering, School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China
中国 合肥 合肥工业大学 食品与生物工程学院 药物科学与工程系
² School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China
中国 南京 中国药科大学生命科学与技术学院
Abstract
As a coagulation factor in the intrinsic coagulation pathway, factor XIa (FXIa) is an effective and safe target for the development of antithrombotic drugs. Many small-molecule FXIa inhibitors have been discovered, some of which are being evaluated in clinical trials. However, none of them have been approved.
In the present study, a highly selective potent FXIa inhibitor with poor solubility reported in our previous work was selected as a lead compound to be further modified to improve FXIa potency and physicochemical properties. The structure-based drug design and structure-activity relationship study led to the discovery of LY8, LY17, and LY25, which demonstrated enhanced FXIa potency and maintained excellent selectivity.
In addition, LY8 exhibited significantly improved aqueous solubility, suggesting that it could be a promising compound to be further evaluated.
Recent progress on mid-infrared and terahertz dual-comb spectroscopy
Zhuoren Wan, Min Li, Binbin Liu, Yu Xia, Yuan Chen, Xiuxiu Zhang, Dongxu Zhu, Yan Dai, Sinan Tao, Hua Li, Ming Yan, Heping Zeng
Opto-Electronic Technology
2026-09-30
Electrically switchable bright-field and interference-synthesized edge-enhanced imaging with a polarization-multiplexed metalens
Xiaotong Li, Junhwa Seong, Yeseul Kim, Kwang-Suk Oh, Shiqi Hu, Le Dai, Harit Keawmuang, Beomha Yang, Minseok Choi, Youngsun Jeon, Cherry Park, Weiyan Li, Tianxu Jia, Han Zhu, Xiaodong Cai, Qi Zheng, Jinhui Shi, Young-Ki Kim, Yuchuan Shao, Trevon Badloe, Junsuk Rho
Opto-Electronic Science
2026-09-20
3D-printed copper water cooling system assisted fabrication of 10.6-μm high-power CO₂ laser resistance reflectors
Hongfei Jiao, Binbin Jiang, Xinshang Niu, Yifan Wang, Dongdong Li, Jun Yu, Xiaochuan Ji, Jingjing Xia, Jinlong Zhang, Xinbin Cheng, Zhanshan Wang
Opto-Electronic Advances
2026-09-15
Ultrafast all-optical modulation of wide-bandwidth pulses enabled by silicon-metasurfaces
Kaloyan Georgiev, Khosro Zangeneh Kamali, Anton A. Trifonov, Giulia Crotti, Lyuben Petrov, Stefan Georgiev, Hristo Iliev, Lei Xu, Unai Arregui Leon, Mohsen Rahmani, Giuseppe Della Valle, Ivan Buchvarov, Dragomir Neshev
Opto-Electronic Advances
2026-09-15
