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

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A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement.

Author: Jianbing WU ¹ ; Duorui JI ¹ ; Weijie JIAO ¹ ; Jian JIA ¹ ; Jiayi ZHU ¹ ; Taijun HANG ² ; Xijing CHEN ³ ; Yang DING ⁴ ; Yuwen XU ⁵ ; Xinglong CHANG ⁶ ; Liang LI ⁶ ; Qiu LIU ⁶ ; Yumei CAO ⁶ ; Yan ZHONG ⁶ ; Xia SUN ⁶ ; Qingming GUO ⁶ ; Tuanjie WANG ⁶ ; Zhenzhong WANG ⁶ ; Ya LING ⁶ ; Wei XIAO ⁶ ; Zhangjian HUANG ¹ ; Yihua ZHANG ¹
Author Information

1. 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.
2. Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
3. Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
4. 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.
5. Crystal Pharmatech Co., Ltd., Suzhou 215123, China.
6. State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China.
Publication Type:Journal Article
Keywords: AAPB; Blood flow improvement; Dual effects; Ischemic stroke; Neuroprotection; Nitric oxide; Pharmacokinetic properties; Safety profiles
From: Acta Pharmaceutica Sinica B 2025;15(2):1070-1083
CountryChina
Language:English
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.