科研队伍

方唯硕1997年毕业于中国协和医科大学,获理学博士学位。1997-1999年美国佛罗里达州立大学博士后;1999年在中国医学科学院药物研究所开始独立研究,历任副研究员、研究员;2001-2002年美国伊利诺伊大学厄巴纳-香槟分校访问学者;2015-2016年美国北卡罗来纳大学教堂山分校访问学者。曾获1999年首届教育部全国高等院校优秀博士学位论文奖和2004年中国药学会施维雅青年药物化学奖,及1996年卫生部科学技术进步一等奖主要完成人之一,2014年教育部自然科学奖二等奖第一完成人。

本实验室的研究方向为活性天然产物的药物化学与化学生物学。近年主要从事两个方面的研究:
(1)微管系统特别是以微管-微管相关蛋白互作为靶的小分子发现,以及在肿瘤和神经退行性疾病治疗中的应用;
(2)天然产物及受天然产物启发的化合物库用于新药发现,涉及的药物靶点有代谢性核受体法尼酯X受体和癌基因MYC。

1. Synthesis and biological evaluation of chalcones and related compounds as farnesoid X receptor (FXR) antagonists. Guoning Zhang, Shuainan Liu, Wenjuan Tan, Ruchi Verma, Yuan Chen, Deyang Sun, Chunming Jia, Na Wang, Yang Xu, Chiwai Wong, Zhufang Shen, Ruitang Deng, Jinsong Liu, Yanqiao Zhang, Weishuo Fang.* European Journal of Medicinal Chemistry 2017, 129: 303-309.
2. Modification of C-seco Taxoids Through Ring Tethering and Substituent Replacement to Seek for Effective Agents Against Tumor Drug Resistance Mediated by -III Tubulin and Pgp Overexpression. Yong Tang, Javier Rodríguez-Salarichs, Yu Zhao, Pei Cai, Juan Estévez-Gallego, Francisco Balaguer-Pérez, Isabel Barasoain, J. Fernando Díaz,* Wei-Shuo Fang*. European Journal of Medicinal Chemistry 2017, 137: 488-503.
3. Design, synthesis and metabolic regulation effect of farnesoid X receptor (FXR) antagonistic benzoxepin-5-ones. Guo-Ning Zhang#, Yi Huan#, Xing Wang, Su-Juan Sun, Zhu-Fang Shen, Wei-Shuo Fang*. Chinese Chemical Letters 2017, 28(7): 1519-1522.
4. Discovery of farnesoid X receptor antagonists based on a library of 3-O-esters of oleanolic acid through diverse substitution design and molecular docking methods. Shao-Rong Wang#, Tingting Xu#, Kai Deng, Chi-Wai Wong, Jinsong Liu, Wei-Shuo Fang*. 2017, Molecules 2017, 22(5): 690-702.
5. A Series of Enthalpically Optimized Docetaxel Analogues Exhibiting Enhanced Antitumor Activity and Water Solubility. Yun-Tao Ma, Yanting Yang, Pei Cai, De-Yang Sun, Pedro A. Sánchez-Murcia, Xiao-Ying Zhang, Wen-Qiang Jia, Lei Lei, Mengqi Guo, Federico Gago, Hongbo Wang,* Wei-Shuo Fang.* Journal of Natural Products 2018, 81(3):524-533.
6. Discovery of a series of selective and cell permeable beta-secretase (BACE1) inhibitors by fragment linking with the assistance of STD-NMR. Wei-Shuo Fang,* De-yang Sun, Shuang Yang, Chen Cheng, Katrin Moschke, Tianqi Li, Shanshan Sun, Stefan Lichtenthaler, Jian Huang, Yinghong Wang.* Bioorganic Chemistry 2019, 92: 103253.
7. Extensive structure modification on luteolin-cinnamic acid conjugates leading to BACE1 inhibitors with optimal pharmacological properties. De-yang Sun, Chen Cheng, Katrin Moschke, Jian Huang, Wei-Shuo Fang.* Molecules 2020, 25(1), 102-122.
8. Taxanes convert regions of perturbed microtubule growth into rescue sites. Ankit Rai, Tianyang Liu, Simon Glauser, Eugene A. Katrukha, Ruddi Rodríguez-García, Wei-Shuo Fang, J. Fernando Díaz, Michel O. Steinmetz, Karl-Heinz Altmann, Lukas C. Kapitein, Carolyn A. Moores, Anna Akhmanova.* Nature Materials 2020, 19(3): 355-365.

1. Wei-Shuo Fang, Deyang Sun, Shuang Yang, Na Guo. β-Secretase (BACE1) Inhibitors from Natural Products. In: P. B. Andrade, P. Valentão and D. M. Pereira (eds) Natural Products Targeting Clinically Relevant Enzymes, Wiley-VCH Verlag, Weinheim, Germany. 2017, p.93-134.
2. Xiao-tian Liang, Wei-shuo Fang (ed.) Medicinal Chemistry of Bioactive Natural Products. Wiley Interscience (Hoboken, NJ, USA), 2006, p.1-440.

1. 2014年,以微管为靶的紫杉烷类分子抗肿瘤耐药应用基础研究,第一完成人,教育部自然科学奖二等奖