李曉康  副教授/博導(dǎo)

Email：xkli@ecust.edu.cn

郵編：200237

通訊地址1：上海市徐匯區(qū)梅隴路130號實(shí)驗(yàn)十八樓431辦公室

通訊地址2：上海市奉賢區(qū)海思路999號實(shí)驗(yàn)五樓309辦公室

【個(gè)人簡介】

      2018年6月畢業(yè)于華東理工大學(xué)藥學(xué)院，獲藥學(xué)博士學(xué)位；2020年10月博士后出站留校工作，加入李劍教授團(tuán)隊(duì)。

      研究方向圍繞臨床未滿足重大疾病新藥創(chuàng)制與精準(zhǔn)診斷，聚焦團(tuán)隊(duì)老藥新用與老藥二次研發(fā)創(chuàng)新策略，形成完善的“老藥先導(dǎo)物發(fā)現(xiàn)→老藥新用研究→新結(jié)構(gòu)二次研發(fā)→新靶標(biāo)機(jī)制研究→臨床前候選PCC確定”技術(shù)體系，用多學(xué)科交叉合作，聚焦重大代謝性慢性，包括酒精性與非酒精性脂肪性肝病（肝損傷與肝臟衰老）、慢性腎衰竭（腎臟衰老）、阿爾茨海默病（腦衰老），以及耐藥微生物感染（耐藥瘧疾、耐藥真菌）等疾病領(lǐng)域，形成經(jīng)驗(yàn)豐富的臨床前候選新藥發(fā)現(xiàn)與評價(jià)體系；此外，結(jié)合熒光探針可視化技術(shù)，構(gòu)建可視化藥效評價(jià)新方法/新模型。

近年來，以第一/通訊作者發(fā)表SCI論文22篇，包括Acta Pharm. Sin. B（2020）、J. Med. Chem.（2016/2021/2022/2024）、Chem. Sci.（2020）、Eur. J. Med. Chem.（2022/2022/2024）等藥學(xué)/化學(xué)領(lǐng)域一區(qū)期刊；申請發(fā)明專利23項(xiàng)（其中PCT專利5項(xiàng)），已授權(quán)專利5項(xiàng)；實(shí)現(xiàn)新功能食品專利授權(quán)轉(zhuǎn)讓1項(xiàng)。作為項(xiàng)目負(fù)責(zé)人主持國家基金2項(xiàng)，省部級基金2項(xiàng)；入選國家高層次青年人才（QB，2025），上海市東方英才（青年，2024）、揚(yáng)帆計(jì)劃（2019）、晨光計(jì)劃（2018）和“超級博士后”激勵(lì)計(jì)劃（2018）。作為研究骨干參與多項(xiàng)國家新藥創(chuàng)制重大專項(xiàng)、國家重點(diǎn)研發(fā)計(jì)劃課題、基金委重點(diǎn)項(xiàng)目等研究項(xiàng)目。講授課程包括本科專業(yè)核心課程《藥物化學(xué)》、專業(yè)選修課《藥物結(jié)構(gòu)優(yōu)化——設(shè)計(jì)策略和經(jīng)驗(yàn)規(guī)則》，參與“十四五”規(guī)劃制藥工程專業(yè)《藥物化學(xué)》章節(jié)編寫。

【學(xué)術(shù)兼職】

1、上海市新藥設(shè)計(jì)重點(diǎn)實(shí)驗(yàn)室副主任

2、《中國藥物化學(xué)雜志》首屆青年編委

3、中醫(yī)藥慢病防治工程委員會委員

4、華東理工大學(xué)新藥研發(fā)青少年創(chuàng)新實(shí)驗(yàn)室（市級），主理人

【研究方向】
    涵蓋藥物化學(xué)、藥理學(xué)、化學(xué)生物學(xué)

1、老藥新用與老藥二次研發(fā)

2、器官衰老相關(guān)疾病候選新藥研發(fā)與新靶標(biāo)機(jī)制解析（肝臟：ALD/NAFLD/MAFLD；腎臟：ARF/CRF）

3、創(chuàng)新中藥活性成分分離鑒定與新靶標(biāo)機(jī)制解析

4、基于病理標(biāo)志物設(shè)計(jì)熒光探針分子并構(gòu)建可視化藥效評價(jià)新方法/新模型

【招生專業(yè)】

  藥學(xué)專業(yè)：博士/碩士（藥物化學(xué)、藥理學(xué)、化學(xué)生物學(xué)、中藥分離等方向）

                   學(xué)碩/博 + 專碩/博

  當(dāng)前招生需求：藥物化學(xué)（具有良好有機(jī)化學(xué)基礎(chǔ)與合成經(jīng)驗(yàn)者）
                     藥理學(xué)（擬開展代謝相關(guān)肝病研究，涉及細(xì)胞、動物水平藥效評價(jià)，中藥活性成

               分分離與結(jié)構(gòu)鑒定、活性分子靶標(biāo)垂釣與機(jī)制研究、臨床轉(zhuǎn)化與產(chǎn)品開發(fā)）

【代表性論文】(^#共同第一作者，*為通訊作者)

[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.