李晓杨

李晓杨

博士

教授

博士生导师

科 室：

药物化学

办公电话：

0532-85902675

 电子邮箱：

lixiaoyang@ouc.edu.cn

联系地址：

山东省青岛市香港东路23号中国海洋大学浮山校区

研究方向：

1.基于靶标的药物设计、合成及活性研究

2.基于表观遗传学靶标的药物发现

3.药物治疗新靶标的发现和验证

个人简介

主要从事基于表观遗传学靶标（如HDAC）、NLRP3等的小分子抑制剂设计、合成及对肿瘤、炎症、代谢性疾病等相关的生物活性评价和药物开发。近年来获评山东省泰山学者青年专家（2022）、山东省优青（2023）、崂山拔尖人才（2021）。主持国家自然科学基金、山东省自然科学基金、山东省重点研发计划子课题等基金项目。以通讯/一作在 J. Med. Chem.、Adv. Sci.、Med. Res. Rev.等杂志发表SCI论文30余篇，授权专利10余项。

教育背景

2011~2016

山东大学

药物化学

博士

2007~2011

山东大学

药学

学士

工作经历

2025-今

中国海洋大学 医药学院

教授

2019~2025

中国海洋大学 医药学院

青年英才第二层次 副教授

2016~2019

美国南卡罗来纳医科大学

博士后

学术兼职

Pharmaceutical Science Advances青年编委、Mar. Drugs.客座编辑

STTT、J Med Chem、APSB、Eur J Med Chem、Bioorg Chem等国际权威期刊审稿人

山东省医学伦理学会类器官和再生医学分会  副主任委员

青岛市药学会药物化学专业委员会   委员

承担课程

药物化学（本科）

高等药物化学（研究生）

研究进展

组蛋白去乙酰化酶（Histone deacetylases, HDACs）通过控制组蛋白乙酰化修饰来调控基因表达，是目前研究最深入的一类表观遗传学调控因子。除了对组蛋白的修饰外，HDAC也通过调节p53、p65、Hsp90、皮动蛋白（cortactin）、Tau蛋白、LC-3、AKT等多种非组蛋白的乙酰化水平控制生理和疾病相关的关键细胞过程，如基因转录，DNA损伤修复，细胞分裂，信号转导，蛋白质折叠，自噬和新陈代谢等。HDAC不同亚型在特定疾病的发生发展中发挥不可替代的作用，如HDAC1、2、3与肿瘤、HDAC6与炎症、HDAC11与代谢性疾病等，因此基于HDAC的药物化学研究是创新药物发现的有效途径。本课题组近年来主要从事HDAC作为肿瘤、炎症、代谢性疾病的靶点发现与验证，选择性HDAC抑制剂的设计和优化，为肿瘤、炎症、代谢性疾病的治疗提供策略。

代表性成果

代表性论文(*corresponding author)：

1.Simin Sun#, Kairui Yue#, Enqiang Liu, Danmei Sheng, Yuxin Chen, Tianqi Li, Aijun Shen, Geng Jia, Yuqi Jiang*, Xiaoyang Li*. Design, Synthesis, and Anti-inflammatory Activity Evaluation for Hydrazide-Based HDAC6 Targeted Protein Degraders. J Med Chem. 2025, 68(22):24519-24545.

2.Kairui Yue#, Simin Sun#, Zequn Yin#, Enqiang Liu, Geng Jia, Yuqi Jiang, Yajun Duan, Yuxin Chen, and Xiaoyang Li*. Development of Hydrazide-Based HDAC6 Selective Inhibitors for Treating NLRP3 Inflammasome-Related Diseases. J Med Chem. 2025, 68(9):9279-9302.

3.Feng Zhang#, Kairui Yue#, Simin Sun, Shengyuan Lu, Geng Jia, Yang Zha, Shuang Zhang, C. James Chou, Chenzhong Liao, Xiaoyang Li*, Yajun Duan*. Targeting Histone Deacetylase 11 with a Highly Selective Inhibitor for the Treatment of MASLD. Adv Sci (Weinh). 2025, 12(15):e2412903

4.Simin Sun#, Zhuoyue Li#, Chao Huang#, Jinyu Liu, Qixin Yu, Xiaolin Jiang, Kairui Yue, Jianchun Zhao, Tongqiang Xu, Yankai Liu, Xiaoyang Li*, Chong Qin*, and Yuqi Jiang*. Discovery of Novel 2,3-Dihydro‑1H‑indene-5-sulfonamide NLRP3 Inflammasome Inhibitors Targeting Colon as a Potential Therapy for Colitis. J. Med. Chem. 2023, 66 (23):16141-16167.

5.Liang Zhang, Kangjing Qi, Jie Xu, Yan Xing, Xuejian Wang, Ling Tong, Zengguo He, Wenfang Xu, Xiaoyang Li*, and Yuqi Jiang*. Design, Synthesis, and Anti-Cancer Evaluation of Novel Cyclic Phosphate Prodrug of Gemcitabine. J. Med. Chem. 2023, 66(6), 4150-4166.

6.Zhuoyue Li#, Yiming Chen#, Xiaolin Jiang#, Penghui Lu, Chengli Wang, Zhimin Li, Xinyue Yu, Zixuan Yang, Shumin Ma, Shanshan Du, Zhengfu Tai, Xiaoyang Li*, Siqi Zhang*, Yuqi Jiang*, and Chong Qin*. Novel Sulfonylurea-Based NLRP3 Inflammasome Inhibitor for Efficient Treatment of Nonalcoholic Steatohepatitis, Endotoxic Shock, and Colitis. J. Med. Chem. 2023, 66 (18):12966-12989.

7.Kairui Yue, Simin Sun, Geng Jia, Mengting Qin, Xiaohan Hou, C. James Chou, Chao Huang, and Xiaoyang Li*. First-in-Class Hydrazide-Based HDAC6 Selective Inhibitor with Potent Oral Anti-Inflammatory Activity by Attenuating NLRP3 Inflammasome Activation. J Med Chem.2022, 65(18):12140-12162.

8.Yuqi Jiang#, Jie Xu#, Kairui Yue#, Chao Huang, Mengting Qin, Dongyu Chi, Qixin Yu, Yue Zhu, Xiaohan Hou, Tongqiang Xu, Min Li, C. James Chou*, and Xiaoyang Li*. Potent Hydrazide-Based HDAC Inhibitors with a Superior Pharmacokinetic Profile for Efficient Treatment of Acute Myeloid Leukemia In Vivo. J Med Chem.2022,65(1):285-302

9.Dongdong Luo, Xiaochun Liu, Leilei Jiang, Zhikun Guo, Yan Lv, Xiaochen Tian, Xiaoyan Wang, Shuxiang Cui, Shengbiao Wan, Ximing Xu*, Xiaoyang Li*, and Xianjun Qu*. Rational Design, Synthesis and Biological Evaluation of Novel S1PR2 Antagonists for Reversing 5-FU-resistance in Colorectal Cancer. J Med Chem. 2022, 65(21),14553-14577.

10.Xiaoyang Li#*, Yuqi Jiang#, Yuri K. Peterson, Tongqiang Xu, Richard A. Himes, Xin Luo, Guilin Yin, Elizabeth S. Inks, Nathan Dolloff, Stephanie Halene, Sherine S. L. Chan, and C. James Chou*. Design of Hydrazide-Bearing HDACIs Based on Panobinostat and Their p53 and FLT3-ITD Dependency in Antileukemia Activity. J Med Chem. 2020,28; 63(10):5501-5525. 

11.Xiaoyang Li*, Richard A. Himes, Lyndsey C. Prosser, Charleston F. Christie, Emma Watt, Sharon F. Edwards, Cameron Metcalf, Peter West, Karen Wilcox, Sherine S. L. Chan*, and C. James Chou*. Discovery of the first Vitamin K analog as a potential treatment of pharmacoresistant seizures. J Med Chem. 2020, 63(11):5865-5878.

12.Liang Zhang#, Geng Jia#, Zhongqiang Li, Simin Sun, Yuxin Chen, Jianchun Zhao, Xuejian Wang, Wenfang Xu, Fanbo Jing*, Yuqi Jiang*, Xiaoyang Li*. Design, synthesis, and anti-cancer evaluation of the novel conjugate of gemcitabine's ProTide prodrug based on CD13. Bioorg Chem. 2025, 157:108293.

13.Baogeng Hou#, Geng Jia#, Zhongqiang Li, Yuqi Jiang, Yuxin Chen, Xiaoyang Li*. Discovery of hydrazide-based PI3K/HDAC dual inhibitors with enhanced pro-apoptotic activity in lymphoma cells. Eur J Med Chem. 2025, 292:117658.

14.Wanting Hao#, Dongdong Luo#,*, Yuqi Jiang, Shengbiao Wan, Xiaoyang Li*. An overview of sphingosine-1-phosphate receptor 2: Structure, biological function, and small-molecule modulators. Med Res Rev. 2024, 44(5):2331-2362.

15.Enqiang Liu#, Yuxin Chen#, Mengting Qin#, Kairui Yue, Simin Sun, Yuqi Jiang, and Xiaoyang Li*. Design, synthesis, and biological activity evaluation of novel HDAC3 selective inhibitors for combination with Venetoclax against acute myeloid leukemia. Eur J Med Chem. 2024, 276:116663.

16.Kairui Yue#, Simin Sun#, Enqiang Liu, Jinyu Liu, Baogeng Hou, Kangjing Qi, C. James Chou, Yuqi Jiang*, and Xiaoyang Li*. HDAC/NAMPT dual inhibitors overcome initial drug-resistance in p53-null leukemia cells. Eur J Med Chem,2024, 266:116127.

17.Geng Jia#, Jinyu Liu#, Xinlu Hou#, Yuqi Jiang*, and Xiaoyang Li*. Biological function and small molecule inhibitors of histone deacetylase 11. Eur J Med Chem. 2024, 276:116634.

18.Chao Huang#, Jinyu Liu#, Yuxin Chen, Simin Sun, Tongtong Kang, Yuqi Jiang*, and Xiaoyang Li*. Discovery of novel biphenyl-sulfonamide analogues as NLRP3 inflammasome inhibitors. Bioorg Chem. 2024, 146:107263.

19.Wanting Hao#, Leyan Wang#, Tongqiang Xu, Geng Jia, Yuqi Jiang, Chong Qin, and Xiaoyang Li*. Marine Cytotoxin Santacruzamate A Derivatives as Potent HDAC1-3 Inhibitors and Their Synergistic Anti-Leukemia Effects with Venetoclax. Mar. Drugs. 2024, 22: 250.

20.Jingjing Deng, Baogeng Hou, Xiaohan Hou, Yuxin Chen, Tao Zhang, Hua Chen, Yuanze Wang, and Xiaoyang Li*.Discovery of benzamide-based PI3K/HDAC dual inhibitors with marked pro-apoptosis activity in lymphoma cells. Eur J Med Chem. 2023, 262:115915.

21.Geng Jia#, Kangjing Qi#, Baogeng Hou, Kairui Yue, Tongqiang Xu, Yuqi Jiang*, and Xiaoyang Li*. Design, synthesis, and biological evaluation of novel HDAC/CD13 dual inhibitors for the treatment of cancer. Eur J Med Chem. 2023, 260:115752.

22.Jiangkun Yan, Kairui Yue, Xuejing Fan, Ximing Xu, Jing Wang, Mengting Qin, Qianer Zhang, Xiaohan Hou, Xiaoyang Li*, Yong Wang*. Synthesis and bioactivity evaluation of ferrocene-based hydroxamic acids as selective histone deacetylase 6 inhibitors. Eur J Med Chem, 2023, 246:115004.

23.Kairui Yue, Mengting Qin, Chao Huang, C James Chou, Yuqi Jiang, Xiaoyang Li*. Comparison of three zinc binding groups for HDAC inhibitors - A potency, selectivity and enzymatic kinetics study. Bioorg Med Chem Lett.2022, 70, 128797.

24.Kairui Yue, Chen Xu, Zhihao Wang, Wandong Liu, Chenyu Liu, Ximing Xu, Yan Xing, Sheng Chen*, Xiaoyang Li*, Shengbiao Wan*. 1,2-Isoselenazol-3(2H)-one derivatives as NDM-1 inhibitors displaying synergistic antimicrobial effects with meropenem on NDM-1 producing clinical isolates. Bioorg Chem. 2022, 129, 106153.

25.Kairui Yue, Xiaohan Hou, Geng Jia, Liang Zhang, Jian Zhang, Leqiao Tan, Xuejian Wang, Zhaolin Zhang, Peixia Li, Wenfang Xu, Xiaoyang Li*, Yuqi Jiang*, Design, synthesis and biological evaluation of hybrid of ubenimex-fluorouracil for hepatocellular carcinoma therapy. Bioorg Chem.2021, 116, 105343

专利

1. 李晓杨; 岳凯瑞; 江余祺; 一种HDAC6抑制剂及其制备方法和应用, 2025-09-12, 中国,ZL202111057941.5 (授权)

2. 李晓杨; 岳凯瑞; 江余祺; 一种选择性组蛋白去乙酰化酶抑制剂及其制备方法和应用, 2025-03-07,中国, ZL202211544602.4 (授权)

3. 李晓杨; 江余祺; 岳凯瑞; 徐文方; 一种组蛋白去乙酰化酶抑制剂及其制备方法和应用, 2022-12-20,中国, ZL202111103830.3 (授权)

4. 李晓杨; 岳凯瑞; 江余祺; 孙思敏; HDAC6抑制剂、制备方法及其应用, 2024-12-31, 中国,202411985255.8 (申请)

5. 李晓杨; 周仲仁; 江余祺; 岳凯瑞; 徐文方; 靶向于HDAC和NAD合成的多靶点抑制剂及其用途, 2022-08-01, WIPO, PCT/CN/2022/109469 (申请)

6. 江余祺; 李晓杨; 黄超; 秦冲; 孙思敏; 于启欣; 徐文方; 一种NLRP3炎症小体抑制剂及其制备方法和应用, 2024-03-19, 中国, ZL202310036113.6 (授权)

7. 张良; 江余祺; 李晓杨; 徐文方; 一种吉西他滨环磷酸酯前药及其制备方法和应用, 2023-08-15, 中国, ZL202111476568.7 (授权)

8. 江余祺; 杨金波; 徐同强; 李晓杨; 秦冲; 张心心; 宋巧玲; 徐文方; 徐锡明; 赵晨阳; 一种替加色罗水溶性有机酸盐及其制备方法与应用, 2023-02-28, 中国, ZL202110134433.6 (授权)

项目课题

1.国家自然科学基金青年基金（82103983），主持，2022-2024年

2.山东省自然科学基金优秀青年基金（ZR2023YQ062），主持，2024-2027年

3.山东省自然科学基金面上项目（ZR2025MS1208），主持，2025-2028年

4.山东省自然科学基金青年基金（ZR2020QH343），主持，2021-2023年

5.山东省泰山学者青年专家，主持，2022-2024年

6.山东省重点研发计划（2020CXGC010503），子课题负责人，2020-2023年

7.中国海洋大学优秀青年科技人才培育计划（B类），主持，2023-2025年

8.青岛市生物医药智库联合基金，主持，2020年

9.青岛市科技计划局（区）会商专项（21-6-1-nsh），主持，2022-2025年