李晓康  副教授/特聘副研究员/硕士生导师

地址：上海市徐汇区梅陇路130号实验十八楼431室

Email：xkli@ecust.edu.cn

邮编：200237

个人简介

      2018年6月毕业于华东理工大学药学院，此后加入cj学者李剑教授团队从事教学科研工作。研究方向主要围绕重大疾病新药创制与精准诊断，立足团队老药（化药和中药）二次研发策略，形成完善的“先导老药的发现（多种策略）→老药新用研究→新结构二次研发→新靶标机制研究→临床前候选药物确定（药效、药代、毒理、成药性等评估）”研究体系，结合荧光探针可视化检测，形成经验丰富的临床前候选新药发现与评价体系，采用多学科交叉合作，聚焦酒精性肝损伤、肝老化、阿尔茨海默病、耐药疟疾等难治性疾病，通过分子机制创新，开发临床前候选药物与诊断工具。近年来，本人以第一/通讯作者在Acta Pharm. Sin. B、J. Med. Chem.、 Chem. Sci.、Eur. J. Med. Chem.、Chin. Chem. Lett.、ACS Chem. Neurosci.、Dyes Pigm.、Bioorg. Med. Chem.等国内外知名学术期刊行发表多篇SCI文章，申请发明专利17项（授权5项）。

      作为负责人主持国家自然科学基金面上项目1项（2021）、国家自然科学基金青年基金1项（2019）、上海市面上项目（2023）、中国博士后科学基金面上项目（2018）；入选上海市青年科技英才扬帆计划（2019）、上海市晨光计划（2018）、上海市“超级博士后”激励计划（2018）。作为研究骨干参与多项国家新药创制重大专项、国家重点研发计划课题、基金委重点项目等研究项目。讲授课程包括本科专业核心课程《药物化学》、专业选修课《药物结构优化——设计策略和经验规则》，参“十四五”规划制药工程专业《药物化学》章节编写。

主要研究方向

1. 老药新用与老药二次研发

2. 基于中草药的新靶标机制研究与新药发现

3. 衰老相关疾病（衰老、肝老化、AD）精准诊断与创新药物研发

4. 靶向PfHDAC1的新型多时期抗耐药疟疾候选药物研发

代表性论文(^#共同第一作者，*为通讯作者)

1. Chao Zhang^#, Lan Wang^#, Yixiang Xu^#, Yunyuan Huang, Junyang Huang, Jin Zhu, Wei Wang, Wangsheng Li, Annan Sun, Xiaokang Li*, Haiyan Zhang*, Jian Li*. Discovery of novel dual RAGE/SERT inhibitors for the potential treatment of the comorbidity of Alzheimer’s disease and depression. Eur. J. Med. Chem.2022, 236, 114347.

   
   

2. Manjiong Wang^#, Tongke Tang^#, Zhenghui Huang, Ruoxi Li, Dazheng Ling, Jin Zhu, Lubin Jiang*, Jian Li*, Xiaokang Li*. Design and synthesis of novel hydroxamic acid derivatives based on quisinostat as promising antimalarial agents with improved safety. Acta Materia Medica2022, 1, 212–223.

   
   

3. Manjiong Wang^#, Tongke Tang^#, Ruoxi Li, Zhenghui Huang, Dazheng Ling, Lulu Zheng, Yan Ding, Taiping Liu, Wenyue Xu, Feng Zhu, Hui Min, Rachasak Boonhok, Fei Mao, Jin Zhu, Xiaokang Li*, Lubin Jiang*, and Jian Li*. Drug Repurposing of Quisinostat to Discover Novel Plasmodium falciparum HDAC1 Inhibitors with Enhanced Triple-Stage Antimalarial Activity and Improved Safety. J. Med. Chem. 2022. 65, 4156−4181.

4. Xiaokang Li^#, Jinwen Li^#, Yunyuan Huang^#, Qi Gong, Yan Fu, Yixiang Xu, Junyang Huang, Haolan You, Dong Zhang, Dan Zhang, Fei Mao, Jin Zhu, Huan Wang*, Haiyan Zhang*, Jian Li*. The novel therapeutic strategy of vilazodone-donepezil chimeras as potent triple-target ligands for the potential treatment of Alzheimer's disease with comorbid depression. Eur. J. Med. Chem. 2022, 229, 114045.

5. Ruoxi Li^#, Dazheng Ling^#, Tongke Tang^#, Zhenghui Huang, Manjiong Wang, Yan Ding, Taiping Liu, Hanwen Wei, Wenyue Xu, Fei Mao, Jin Zhu, Xiaokang Li*, Lubin Jiang*, Jian Li*. Discovery of novel P. falciparum HDAC1 inhibitors with dual-stage anti-malarial potency and improved safety based on the clinical anticancer drug candidate quisinostat. J. Med. Chem. 2021, 64, 2254.

6. Ruoxi Li^#, Dazheng Ling^#, Tongke Tang^#, Zhenghui Huang, Manjiong Wang, Fei Mao, Jin Zhu, Lubin Jiang*, Jian Li*, Xiaokang Li*. Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents. Chin. Chem. Lett. 2021, 32, 1660−1664.

7. Xiaokang Li^#, Jian Lu^#, Yixiang Xu^#, Jiaying Wang, Xiaoxia Qiu, Lei Fan, Baoli Li, Wenwen Liu, Fei Mao, Jin Zhu, Xu Shen*, Jian Li*. Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease. Acta Pharm. Sin. B 2020, 10, 646–666.

8. Xiaokang Li^#, Wenjing Qiu^#, Jinwen Li^#, Xi Chen^#, Yulu Hu, Ying Gao, Donglei Shi, Xinming Li, Huiling Lin, Zelan Hu, Guoqiang Dong, Chunquan Sheng, Bei Jiang, Conglong Xia, Chu-Young Kim, Yuan Guo*, Jian Li*. First-generation species-selective chemical probes for fluorescence imaging of human senescence-associated β-galactosidase. Chem. Sci. 2020, 11, 7292.（封面文章）

9. Wenjing Qiu^#, Xiaokang Li^#, Donglei Shi, Xinming Li, Ying Gao, Fei Mao, Yuan Guo, Jian Li*. A rapid-response near-infrared fluorescent probe with a large Stokes shift for senescence-associated -galactosidase activity detection and imaging of senescent cells. Dyes Pigm. 2020, 182, 108657.

10. Yixiang Xu^#, Jian Zhang^#, Huan Wang^#, Fei Mao, Keting Bao, Wenwen Liu, Jin Zhu, Xiaokang Li*, Haiyan Zhang*, and Jian Li*. Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase and Monoamine Oxidase B as Potential Anti-Alzheimer's Disease Agents. ACS Chem. Neurosci. 2019, 10, 482−496.

11. Jin Li^#, Xiaokang Li^#, Jianbo Jia^#, Xi Chen, Yinjuan Lv, Yuan Guo*, and Jian Li*. A ratiometric near-infrared fluorescence strategy based on spiropyran in situ switching for tracking dynamic changes of live-cell lysosomal pH. Dyes Pigm. 2019, 66, 433–442.

12. Wenwen Liu^#, Huan Wang^#, Xiaokang Li^#, Yixiang Xu, Jian Zhang, Wei Wang, Qi Gong, Xiaoxia Qiu, Jin Zhu, Fei Mao*, Haiyan Zhang*, Jian Li*. Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment. Bioorg. Med. Chem. 2018, 26, 3117–3125.

13. Wei Ni^#, Huan Wang^#, Xiaokang Li^#, Xinyu Zheng, Manjiong Wang, Jian Zhang, Qi Gong, Dazheng Ling, Fei Mao*, Haiyan Zhang*, and Jian Li*. Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5). ACS Chem. Neurosci. 2018, 9, 1625−1636.

14. Xiaokang Li^#, Yahui Huang^#, Junfei Cheng^#, Lingling Zhang, Fei Mao, Jin Zhu, Chunquan Sheng*, Jian Li*. Discovery of novel Syk/PDGFR-α/c-Kit inhibitors as multi-targeting drugs to treat rheumatoid arthritis. Bioorg. Med. Chem. 2018, 26, 4375–4381.

15. Xiaokang Li^#, Huan Wang^#, Yixiang Xu, Wenwen Liu, Qi Gong, Wei Wang, Xiaoxia Qiu, Jin Zhu, Fei Mao, Haiyan Zhang *, and Jian Li *. Novel Vilazodone–Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation. ACS Chem. Neurosci. 2017, 8, 2708−2721.

16. Xiaokang Li^#, Huan Wang^#, Zhengyu Lu, Xinyu Zheng, Wei Ni, Jin Zhu, Yan Fu, Fulin Lian, Naixia Zhang, Jian Li*, Haiyan Zhang*, and Fei Mao*. Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents. J. Med. Chem. 2016, 59, 8326–8344.

17. Xiaokang Li, Wei Ni, Fei Mao, Wei Wang*, Jian Li*. A Metal-free Approach to 3-Aryl-3-hydroxy-2-oxindoles by Treatment of 3-Acyloxy-2-oxindoles with Diaryliodonium Salts. Chem. Asian J. 2016, 11, 226–230.