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李晓康



李晓康  博士/副教授/博

Emailxkli@ecust.edu.cn

邮编200237

通讯地址1:上海市徐汇区梅陇路130号实验十八楼431办公室

通讯地址2:上海市奉贤区海思路999号实验五楼309办公室



【个人简介】


      20186月毕业于华东理工大学药学院,获药学博士学位,导师李剑教授。随后加入华东理工大学药学博士后科研流动站从事博士后研究,合作导师为蒋华良院士。202010月出站留校工作,加入李剑教授团队。

      研究方向围绕临床未满足重大疾病新药创制与精准诊断,聚焦团队老药新用与老药二次研发创新策略,形成完善的“老药先导物发现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PCC确定”技术体系,用多学科交叉合作,聚焦重大代谢性慢性,包括酒精性与非酒精性脂肪性肝病(肝损伤与肝脏衰老)、慢性肾衰竭(肾脏衰老)、阿尔茨海默病(脑衰老),以及耐药微生物感染(耐药疟疾、耐药真菌)等疾病领域,形成经验丰富的临床前候选新药发现与评价体系;此外,结合荧光探针可视化技术,构建可视化药效评价新方法/新模型。

近年来,以第一/通讯作者发表SCI论文22篇,包括Acta Pharm. Sin. B2020)、J. Med. Chem.2016/2021/2022/2024)、Chem. Sci.2020)、Eur. J. Med. Chem.2022/2022/2024)等药学/化学领域一区期刊;申请发明专利23项(其中PCT专利5项),已授权专利5项;实现新功能食品专利授权转让1项。作为项目负责人主持国家基金2项,省部级基金2项;入选上海市东方英才(青年,2024)、扬帆计划(2019)、晨光计划(2018)和“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》,参与“十四五”规划制药工程专业《药物化学》章节编写。


【学术兼职】

1、上海市新药设计重点实验室副主任

2、《中国药物化学杂志》首届青年编委

3、中医药慢病防治工程委员会委员

4、华东理工大学新药研发青少年创新实验室(市级),主理人



【研究方向】
    
涵盖药物化学、药理学、化学生物学

1、老药新用与老药二次研发

2、器官衰老相关疾病候选新药研发与新靶标机制解析肝脏ALD/NAFLD/MAFLD肾脏ARF/CRF

3、创新中药活性成分分离鉴定与新靶标机制解析

4、基于病理标志物设计荧光探针分子并构建可视化药效评价新方法/新模型


【招生专业】

  药学专业:博士/硕士(药物化学、药理学、化学生物学、中药分离等方向)


【代表性论文】(#共同第一作者,*为通讯作者)


[1]     Yunyuan Huang#, Xin Chen#, Jin Yang#, Yue Yao, Manjiong Wan, Taotao Lu, Xiao Li, Jiqun Wang, Sicong Qiao, Donglei Shi, Xiaoking Li*, Jian Li*, Yixiang Xu*. Methoxsalen Identified through Synergistic Network Virtual Screening and Experimental Validation. J. Chem. Inf. Model.2024, https://doi.org/10.1021/acs.jcim.4c00670.

[2]     Haolan You#, Yihe Song#, Yi Yang#, Xicheng Wang, Shiqi Pan, Junyang Huang, Qiqi Shao, Donglei Shi, Baoli Li*, Jian Li*, Xiaokang Li*. Rational design of a high-affinity fluorescent probe for visualizing monitoring the amyloid β clearance effect of anti-Alzheimer's disease drug candidates. Eur. J. Med. Chem.2024, 278, 116800.

[3]     Xiangran Lu#, Rongrong Wang#, Yao Yu#, Jinlian Wei, Yixiang Xu, Luoyifan Zhou, Fei Mao, Jian Li*, Xiaokang Li*, and Xinming Jia*. Drug Repurposing of ACT001 to Discover Novel Promising Sulfide Prodrugs with Improved Safety and Potent Activity for Neutrophil-Mediated Antifungal Immunotherapy. J. Med. Chem. 2024, 67, 5783−5799.

[4]     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.

[5]     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.

[6]     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.

[7]     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.

[8]     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.

[9]     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.

[10]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. B2020, 10, 646–666.

[11]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)

[12]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.

[13]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.

[14]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.

[15]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.

[16]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.

[17]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.

[18]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.

[19]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.

[20]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.