创新药物非临床药物代谢及PKPD研究北京市重点实验室

个人简介

主要从事先导物药代特性早期评价及新方法研究、新药临床前药代动力学研究、药物代谢酶和转运蛋白调控的分子机制和生物学效应研究等。担任中国药理学会药物代谢专业委员会委员，北京药理学会药物代谢专业委员会委员。参与完成的5个1.1类新药（抗慢性肾功能不全药硝克柳胺，抗凝血药SAR107375E，抗结核药吡法齐明和OTB-658，PD-L1抑制剂艾姆地芬）已进入临床研究。主持和参与多项科研项目，包括国家科技部重大新药创制专项、国家自然科学基金、协和青年科研基金、中央级公益性科研院所基本科研业务费专项基金、青年医学教育学者计划项目等。发表科研论文30余篇，参编论著3部，2015年获教育部自然科学二等奖。

研究方向

1. 新药临床前药代动力学及PK/PD研究
2. 血脑屏障与药物转运研究
3. 药物代谢酶和转运蛋白相关的药物相互作用机制研究

发表论文

1. Jiang J#, Zou X#, Liu Y, Liu X, Dong K, Yao X, Feng Z, Chen X, Sheng L*, Li Y. Simultaneous Determination of a Novel PD-L1 Inhibitor, IMMH-010, and Its Active Metabolite, YPD-29B, in Rat Biological Matrices by Polarity-Switching Liquid Chromatography-Tandem Mass Spectrometry: Application to ADME Studies. Front Pharmacol. 2021;12:677120.
2. Wang Y#, Liu X#, Zou X, Wang S, Luo L, Liu Y, Dong K, Yao X, Li Y, Chen X*, Sheng L*. Metabolism and Interspecies Variation of IMMH-010, a Programmed Cell Death Ligand 1 Inhibitor Prodrug. Pharmaceutics. 2021;13(5):598.
3. Jiang J#, Liu Y#, Liu X, Zhang D, Huang H, Wang B*, Sheng L*, Li Y. Simultaneous determination of a novel oxazolidinone anti-tuberculosis OTB-658 and its metabolites in monkey blood by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2021;1167:122552.
4. Liu X, Jiang J, Jin X, Liu Y, Xu C, Zhang J, Shi J, Sheng L*, Li Y. Simultaneous determination of YZG-331 and its metabolites in monkey blood by liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2021;193:113720.
5. Wen H#, Liu Y#, Wang S, Wang T, Zhang G, Chen X, Li Y, Cui H, Lai F*, Sheng L*. Design and Synthesis of Indoleamine 2,3-Dioxygenase 1 Inhibitors and Evaluation of Their Use as Anti-Tumor Agents. Molecules. 2019;24(11):2124.
6. Zhang Z#, Liu D#, Jiang J, Song X, Zou X, Chu S, Xie K, Dai J, Chen N*, Sheng L*, Li Y. Metabolism of IMM-H004 and Its Pharmacokinetic-Pharmacodynamic Analysis in Cerebral Ischemia/Reperfusion Injured Rats. Front Pharmacol. 2019;10:631.
7. Jiang J, Zhang Z, Zou X, Wang R, Bai J, Zhao S, Fan X, Sheng L*, Li Y. Determination of IMM-H004 and its active glucuronide metabolite in rat plasma and Ringer's solution by ultra-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1074-1075:16-24.
8. Wu X, Zhang Q, Guo J, Jia Y, Zhang Z, Zhao M, Yang Y, Wang B, Hu J, Sheng L*, Li Y*. Metabolism of F18, a Derivative of Calanolide A, in Human Liver Microsomes and Cytosol. Front Pharmacol. 2017;8:479.
9. Liu Z#, Yang Y#, Sheng L*, Li Y. Interspecies Variation of In Vitro Stability and Metabolic Diversity of YZG-331, a Promising Sedative-Hypnotic Compound. Front Pharmacol. 2017;8:527.
10. Liu X, Zhao M, Mi J, Chen H, Sheng L*, Li Y*. Protective Effect of Bicyclol on Anti-Tuberculosis Drug Induced Liver Injury in Rats. Molecules. 2017;22(4):524.
11. Zhang Z, Wu X, Zhao M, Yang Y, Wang Y, Hu J, Wang B, Sheng L*, Li Y*. Determination of IMM-H004, a novel neuroprotective agent, in rat plasma and brain tissue by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2017;1048:49-55.
12. Yang F#, Wang B#, Liu Z, Xia X, Wang W, Yin D, Sheng L*, Li Y. Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human. Front Pharmacol. 2017;8:683.
13. Liu Z, Mi J, Yang S, Zhao M, Li Y, Sheng L*. Effects of P-glycoprotein on the intestine and blood-brain barrier transport of YZG-331, a promising sedative-hypnotic compound. Eur J Pharmacol. 2016;791:339-347.
14. Zhang G, Sheng L, Hegde P, Li Y, Aldrich CC*. 8-cyanobenzothiazinone analogs with potent antitubercular activity. Med Chem Res. 2021:1-10.
15. Sun Y, Fu R, Lin S, Zhang J, Ji M, Zhang Y, Wu D, Zhang K, Tian H, Zhang M, Sheng L, Li Y, Jin J*, Chen X*, Xu H*. Discovery of new thieno[2,3-d]pyrimidine and thiazolo[5,4-d]pyrimidine derivatives as orally active phosphoinositide 3-kinase inhibitors. Bioorg Med Chem. 2021;29:115890.
16. Zhou C, Lai F, Sheng L, Chen X, Li Y, Feng Z*. Design, Synthesis and Biological Evaluation of Phenyl Urea Derivatives as IDO1 Inhibitors. Molecules. 2020;25(6):1447.
17. Zhao H, Wang B, Fu L, Li G, Lu H, Liu Y, Sheng L, Li Y, Zhang B, Lu Y, Ma C, Huang H*, Zhang D*, Lu Y*. Discovery of a Conformationally Constrained Oxazolidinone with Improved Safety and Efficacy Profiles for the Treatment of Multidrug-Resistant Tuberculosis. J Med Chem. 2020;63(17):9316-9339.
18. Zhao W, Wang B, Liu Y, Fu L, Sheng L, Zhao H, Lu Y, Zhang D*. Design, synthesis, and biological evaluation of novel 4H-chromen-4-one derivatives as antituberculosis agents against multidrug-resistant tuberculosis. Eur J Med Chem. 2020;189:112075.
19. Li G, Meng B, Yuan B, Huan Y, Zhou T, Jiang Q, Lei L, Sheng L, Wang W, Gong N, Lu Y, Ma C, Li Y, Shen Z*, Huang H*. The optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119. Eur J Med Chem. 2020;188:112017.
20. Du T, Lin S, Ji M, Xue N, Liu Y, Zhang Z, Zhang K, Zhang J, Zhang Y, Wang Q, Sheng L, Li Y, Lu D*, Chen X*, Xu H*. A novel orally active microtubule destabilizing agent S-40 targets the colchicine-binding site and shows potent antitumor activity. Cancer Lett. 2020;495:22-32.
21. Lin S, Wang C, Ji M, Wu D, Lv Y, Zhang K, Dong Y, Jin J, Chen J, Zhang J, Sheng L, Li Y, Chen X*, Xu H*. Discovery and Optimization of 2-Amino-4-methylquinazoline Derivatives as Highly Potent Phosphatidylinositol 3-Kinase Inhibitors for Cancer Treatment. J Med Chem. 2018;61(14):6087-6109.
22. Lin S, Wang C, Ji M, Wu D, Lv Y, Sheng L, Han F, Dong Y, Zhang K, Yang Y, Li Y, Chen X*, Xu H*. Discovery of new thienopyrimidine derivatives as potent and orally efficacious phosphoinositide 3-kinase inhibitors. Bioorg Med Chem. 2018;26(3):637-646.
23. Zhao H, Lu Y, Sheng L, Yuan Z, Wang B, Wang W, Li Y, Ma C, Wang X, Zhang D*, Huang H*. Discovery of Fluorine-Containing Benzoxazinyl-oxazolidinones for the Treatment of Multidrug Resistant Tuberculosis. ACS Med Chem Lett. 2017;8(5):533-537.
24. Zhang S, Ma J, Sheng L, Zhang D, Chen X*, Yang J, Wang D. Total Coumarins from Hydrangea paniculata Show Renal Protective Effects in Lipopolysaccharide-Induced Acute Kidney Injury via Anti-inflammatory and Antioxidant Activities. Front Pharmacol. 2017;8:872.

专著

1. 《应用分子药理学》第2版（第十三章药物代谢酶与转运蛋白的调控及分子机制），王晓良主编，中国协和医科大学出版社，2015.
2. 《药理学研究的新技术与新方法》（第八章 CYP450高表达体系在药理学研究中的应用），陈晓光主编，中国协和医科大学出版社，2014.

专利

1. 一类邻位羰基氨基取代苯衍生物的制备方法和用途. 申请号：201910263113.3.
2. N-酰基磺酰胺盐类FBPase抑制剂、其制备方法、药物组合物及用途. 申请号：201811481436.1.
3. 含有哌嗪酮的喹唑啉二酮盐类化合物、其制备方法、药物组合物及用途. 申请号：201811481275.6.
4. 吡咯-2-甲酰胺类化合物及其制备方法和用途. 申请号：201880056468.9.
5. 一种香豆素衍生物代谢产物的制备及其在防治脑缺血和阿尔茨海默病中的应用. 申请号：201810317196.5.
6. N6取代腺苷衍生物和 N6取代腺嘌呤衍生物及其用途. 申请号：200980162826.5.

科技奖励

1.2015年，以微管为靶的紫杉烷类分子抗肿瘤耐药应用基础研究，教育部自然科学二等奖，排名11.