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副研究员

张文轩

职 称:副研究员

所属科室:新药开发研究室

导师类别:硕士生导师

联系方式:wxzhang@imm.ac.cn

所属重点实验室:

个人简介

毕业于北京大学药学院,获得本科和博士学位,现任中国医学科学院&北京协和医学院药物研究所副研究员、新药开发研究室副主任,兼任北京药学会药物化学专业委员会委员。主要从事临床亟需创新药物研究和开发工作,包括治疗耐药细菌感染、肿瘤以及代谢性疾病等活性先导物的结构优化及成药性评价。发现了抗耐药细菌感染候选药物ZXT-4-23及SAL-098、WHN-088等多个具有开发前景的抗肿瘤活性化合物。作为药物化学专题负责人,完成了新型调血脂候选药物IMM-H007(准备开展II期临床试验)和治疗非酒精性肝炎(NASH)候选药物IMM-H014(正在开展I期临床试验)的原料药工艺开发和注册申报工作,上述项目均已成功实现技术成果转化。作为主要发明人和完成人申请国际专利3项,国内专利20余项(已获得授权15项),已在Nat Commun., Acta Pharmaceutica Sinica B, J. Med. Chem., Eur. J. Med. Chem.,《药学学报》等国内外重要期刊上发表论文40余篇。作为课题负责人获得国家自然科学基金、国家外专局项目、北京市自然科学基金、北京协和医学院青年基金和中央高校基本科研业务费等基金支持支持,同时参与“十三五”重大新药创制科技重大专项(2项),中国医学科学院医学与健康科技创新工程重大协同创新项目(3项)。

研究方向

1、 治疗耐药细菌感染、耐药肿瘤以及代谢性疾病等活性先导物的结构优化和成药性评价。
2、 化学原料药合成工艺开发与注册申报。

发表论文

抗耐药菌感染方向
1. Xintong Zhao,# Jing Feng,# Jie Zhang,# Zunsheng Han, Yuhua Hu, Hui-Hui Shao, Tianlei Li, Jie Xia, Kangfan Lei, Weiping Wang, Fangfang Lai, Yuan Lin, Bo Liu, Kun Zhang, Chi Zhang, Qingyun Yang, Xinyu Luo, Hanyilan Zhang, Chuang Li, Wenxuan Zhang,* Song Wu*. Discovery and druggability evaluation of pyrrolamide-type GyrB/ParE inhibitor against drug-resistant bacterial infection[J]. Acta Pharmaceutica Sinica B, 2023, 13(12): 4945-4962. (back cover).
2. Zihao Zhu#, Cantong Chen#, Jie Zhang, Fangfang Lai*, Jing Feng, Guangxu Wu, Jie Xia, Wenxuan Zhang, Zunsheng Han, Chi Zhang, Qingyun Yang, Yuchen Wang, Bo Liu, Tianlei Li*, and Song Wu*Exploration and Biological Evaluation of 1,3-Diamino-7 H -pyrrol[3,2- f ]quinazoline Derivatives as Dihydrofolate Reductase Inhibitors, J. Med. Chem., 2023, 66, 20, 13946–13967.
3. Hongfa Lv#, Zihao Zhu#, Chenliang Qian, Tianlei Li, Zunsheng Han, Wenxuan Zhang, Xinxin Si, Jianfeng Wang, Xuming Deng, Li Li, Tianqi Fang, Jie Xia*, Song Wu*, Yonglin Zhou*, Discovery of isatin-β-methyldithiocarbazate derivatives as New Delhi metallo- β-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates, Biomedicine & Pharmacotherapy, 2023,166,115439.
4. Guangxu Wu#, Zihao Zhu#, Jishun Li, Xinyu Luo, Wenyong Zhu, Guoyang Liao , Jie Xia, Wenxuan Zhang, Weidong Pan, Tianlei Li*, Song Wu*, Design, synthesis and antibacterial evaluation of pleuromutilin derivatives. Bioorganic & Medicinal Chemistry, 2022, 59 116676.
5. 赵欣彤, 李天磊, 张文轩*, 吴 松*,铁离子载体-抗生素偶联物的研究进展,药学学报,2021, 56(11): 3004 -3013. (综述)
6. 胡宇华, 赵欣彤, 李天磊, 吴 松, 张文轩*, 噁唑烷酮类抗菌药物研究进展, 药学学报, 2022, 57(11): 3276-3291. (综述)
7. 雷康璠, 吴 松, 张文轩*,抗鲍曼不动杆菌药物研究进展,药学学报, 2023(综述).
抗肿瘤方向(靶向肿瘤干细胞)
1. Lei Tang#, Wenfang Duan# Chi Zhang#, Yulu Shi, Wenlian, Kangfan Lei, Wenxuan Zhang*, Song Wu*, Jihong Zhang*, Potent salinomycin C20-O-alkyl oxime derivative SAL-98 effciently inhibits tumor growth and metastasis by affecting Wnt/β-catenin signal pathway, Biochemical Pharmacology, 2023, 214, 115666.
2. Qihong Yang #, Tong Qin #, Tao An #, Hongna Wu, Gang Xu, Jin Xiang, Kangfan Lei, Shaohua Zhang, Jie Xia, Guifeng Su, Dan Wang, Minggao Xue, Lingmei Kong, Wenxuan Zhang*, Song Wu*, Yan Li*, Novel PORCN inhibitor WHN-88 targets Wnt/β-catenin pathway and prevents the growth of Wnt-driven cancers, European Journal of Pharmacology, 2023, 945, 175628.
3. Bo Li,# Jun Wu,# Lei Tang,# Xu Lian, Zhongwen Li, Wenfang Duan, Tong Qin, Xintong Zhao, Yuhua Hu, Chi Zhang, Tianlei Li, Jie Hao, Wenxuan Zhang,* Jihong Zhang* and Song Wu*, Synthesis and anti-tumor activity evaluation of salinomycin C20-O-alkyl/benzyl oxime derivatives, Org. Biomol. Chem., 2022, 20, 870.
4. Hongna Wu#, Jun Wu#, Tong Qin, Xu Lian, Zhongwen Li, Baojie Guo, Jie Hao, Qi Zhou, Tianlei Li, Wenxuan Zhang⁎, Song Wu⁎, The structure optimization of dicarboximide-phenylpyridine conjugates as inhibitor of Wnt signaling Pathway, Chemistry select. 2020,5, 13795 – 13799.
5. Hongna Wu #, Jun Wu#, Wenxuan Zhang*, Zhongwen Li, Jinhui Fang, Xu Lian, Tong Qin, Jie Hao, Qi Zhou, Song Wu*. Discovery and structure-activity relationship study of phthalimide- phenylpyridine conjugate as inhibitor of Wnt pathway, Bioorg. Med. Chem. Lett., 2019, 29: 870~872.
代谢性疾病方向
1. Hui Hui Guo#, Chen Lin Feng #, Wenxuan Zhang#, Zhi-Gang Luo#, Hong-Juan Zhang, Ting-Ting Zhang, Chen Ma, Yun Zhan, Rui Li, Song Wu, Zeper Abliz, Cong Li, Xiao-Lin Li, Xiao-Lei Ma, Lu-Lu Wang*, Wen-Sheng Zheng*, Yan-Xing Han* & Jian-Dong Jiang*. Liver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic diseases. Nat Commun., 2019, 10(1): 1981.
2. Xiaolei Ma#, Xiaoyou Yu#, Rui Li#, Jinjin Cui, Haoyang Yu, Ling Ren, Jiandong Jiang, Wenxuan Zhang,* Lulu Wang*, Berberine-silybin salt achieves improved anti-nonalcoholic fatty liver disease effect through regulating lipid metabolism[J]. Journal of Ethnopharmacology, 2024, 319: 117238.
3. Tong Qin#, Xuefeng Gao#, Lei Lei, Jing Feng, Wenxuan Zhang, Yuhua Hu, Zhufang Shen, Zhenming Liu, Yi Huan*, Song Wu*, Jie Xia*, Liangren Zhang. Machine learning-and structure-based discovery of a novel chemotype as FXR agonists for potential treatment of nonalcoholic fatty liver disease [J]. European Journal of Medicinal Chemistry, 2023: 115307.
4. Tong Qin#, Xuefeng Gao#, Lei Lei, Wenxuan Zhang, Jing Feng, Xing Wang, Zhufang Shen, Zhenming Liu, Yi Huan*, Song Wu*, Jie Xia*, Liangren Zhang. Structural optimization and biological evaluation of 1-adamantylcarbonyl-4-phenylpiperazine derivatives as FXR agonists for NAFLD [J]. European Journal of Medicinal Chemistry, 2023, 245: 114903.

专著

专利

近期授权专利(主要发明人)
1. 吴松,张文轩,赵欣彤,李天磊,夏杰,杨庆云,张驰,韩遵圣,冯靖,张洁,张坤,刘博,连旭,朱子豪,邵会会,王越,胡宇华, 吡咯酰哌啶胺类化合物及其用途,202110656714.8
2. 王璐璐,张文轩,蒋建东,吴松,一种盐酸小檗碱和水飞蓟宾形成的盐、其制备方法和应用,ZL202110460032.X
3. 吴松,孙华,张金兰,张文轩,王喆,杨庆云,姜琳,陈子涵,申静,张洁,张驰,韩遵圣,秦通,张媛媛,一种左旋双环吗啉盐、制备方法和用途,ZL201911190936.4, PCT/CN2020/115410
4. 吴松,李艳,张文轩,安涛,武红娜,申静,连旭,秦通,吡啶酮酰联芳基胺类化合物及其用途,ZL201910171194.4
5. 吴松,夏杰,闻刚,冯波,贾雨晴,张文轩,戚燕,杨庆云,张驰, 1-取代苯甲酰基-4-酯酰基氨基硫脲类衍生物、制备方法及作为抗菌药物的用途,ZL201810091202.X
6. 吴松,周琪,张文轩,吴骏,武红娜,王柳,郝捷,调节WNT信号通路的酰胺类化合物及其用途,ZL201711263401.6.
7. 吴松,周琪,张文轩,吴骏,李波,连旭,王柳,郝捷,盐霉素肟醚生物、其制备方法和抗肿瘤用途,PCT/CN2017/085516. 公开日:2017.11.30
8. 吴松,周琪,张文轩,吴骏,李波,王柳,郝捷,盐霉素肟及肟醚生物以及制备方法和抗肿瘤用途,ZL201610347806.7.
9. 吴松,杜冠华,张文轩,何国荣,李莉,C20位差向异构化盐霉素及其酰化衍生物以及制备方法和抗肿瘤用途,ZL201610922564.X.
10. 吴松,孙华,张文轩,张金兰,张丹,王少媛,武丽萍,童元峰,刘宁,一种双环醇类衍生物及其制备和应用,ZL201610922563.5.

科技奖励

《GyrB/ParE双靶点抑制剂抗耐药细菌感染创新药物ZXT-4-23的研发》(吴松团队)获得第二届“未来之星”生物医药创新成果转化项目大赛决赛一等奖