Acta Pharmaceutica Sinica B (Feb 2025)
A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement
- Jianbing Wu,
- Duorui Ji,
- Weijie Jiao,
- Jian Jia,
- Jiayi Zhu,
- Taijun Hang,
- Xijing Chen,
- Yang Ding,
- Yuwen Xu,
- Xinglong Chang,
- Liang Li,
- Qiu Liu,
- Yumei Cao,
- Yan Zhong,
- Xia Sun,
- Qingming Guo,
- Tuanjie Wang,
- Zhenzhong Wang,
- Ya Ling,
- Wei Xiao,
- Zhangjian Huang,
- Yihua Zhang
Affiliations
- Jianbing Wu
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China
- Duorui Ji
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China
- Weijie Jiao
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacy, Henan Province Hospital of Traditional Chinese Medicine, the Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450002, China
- Jian Jia
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China; Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai 201203, China
- Jiayi Zhu
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China
- Taijun Hang
- Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China
- Xijing Chen
- Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China
- Yang Ding
- Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China
- Yuwen Xu
- Crystal Pharmatech Co., Ltd., Suzhou 215123, China
- Xinglong Chang
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Liang Li
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Qiu Liu
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Yumei Cao
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Yan Zhong
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Xia Sun
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Qingming Guo
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Tuanjie Wang
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Zhenzhong Wang
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Ya Ling
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China
- Wei Xiao
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; Nanjing University of Chinese Medicine, Nanjing 210023, China; Corresponding authors.
- Zhangjian Huang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China; Corresponding authors.
- Yihua Zhang
- State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China; Corresponding authors.
- Journal volume & issue
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Vol. 15,
no. 2
pp. 1070 – 1083
Abstract
Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.
