A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement
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-improv...
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| Format: | Article |
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Elsevier
2025-02-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383525000048 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jianbing Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e0e2fb65bb9d4aa1a5b437207d73022b |
| institution | DOAJ |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-e0e2fb65bb9d4aa1a5b437207d73022b2025-08-20T02:47:37ZengElsevierActa Pharmaceutica Sinica B2211-38352025-02-011521070108310.1016/j.apsb.2024.12.042A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvementJianbing Wu0Duorui Ji1Weijie Jiao2Jian Jia3Jiayi Zhu4Taijun Hang5Xijing Chen6Yang Ding7Yuwen Xu8Xinglong Chang9Liang Li10Qiu Liu11Yumei Cao12Yan Zhong13Xia Sun14Qingming Guo15Tuanjie Wang16Zhenzhong Wang17Ya Ling18Wei Xiao19Zhangjian Huang20Yihua Zhang21State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaState 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, ChinaState 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, ChinaState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaDepartment of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, ChinaClinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, ChinaKey Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, ChinaCrystal Pharmatech Co., Ltd., Suzhou 215123, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, ChinaState 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.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.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.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.http://www.sciencedirect.com/science/article/pii/S2211383525000048Ischemic strokeNitric oxideAAPBNeuroprotectionBlood flow improvementDual effects |
| spellingShingle | 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 A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement Acta Pharmaceutica Sinica B Ischemic stroke Nitric oxide AAPB Neuroprotection Blood flow improvement Dual effects |
| title | A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement |
| title_full | A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement |
| title_fullStr | A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement |
| title_full_unstemmed | A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement |
| title_short | A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement |
| title_sort | novel anti ischemic stroke candidate drug aapb with dual effects of neuroprotection and cerebral blood flow improvement |
| topic | Ischemic stroke Nitric oxide AAPB Neuroprotection Blood flow improvement Dual effects |
| url | http://www.sciencedirect.com/science/article/pii/S2211383525000048 |
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