课题组长

张翱 (兼职PI)

职位:特聘教授

电子邮箱:ao6919zhang@sjtu.edu.cn

办公地点:上海市东川路800号上海交通大学药学院6号楼501室

电话:021-54745704

个人网页/课题组主页地址:

研究方向:

  • 长期致力于药物化学技术创新推动的新药发现研究,尤其是通过基于靶标变构位点药物设计技术、泛素介导的靶向蛋白降解技术、蛋白翻译后修饰动态调控技术、DNA编码集中库设计技术、基因转录模拟物设计、药物分子后期修饰等药物设计新技术,结合基于药物代谢及血脑屏障通透性等药物结构优化策略,在与化学生物学、结构生物学和药理学等合作基础上,建立了多学科联合攻关的创新药物研究团队,聚焦新靶标新分子实体原创新药发现的药物化学和化学生物学研究、难靶蛋白的药物设计、分子靶向个性化药物研究等领域,取得了显著成绩。

教育背景:

  • 1997.11-2000.12      上海有机化学研究所,理学博士

  • 1992.09-1995.07      南开大学,硕士

  • 1988.09-1992.07      西华师范大学,学士

工作经历:

  • 2020.05-至今    上海交通大学药学院,教授

  • 2006.02-2020.04  中科院上海药物研究所,研究员

  • 2004.04-2006.02  美国哈佛大学医学院,讲师、 助理主任

  • 2002.04-2004.03  美国哈佛大学医学院,博士后

  • 2001.02-2002.03  美国乔治城大学医学中心,博士后

  • 1995.07-1997.10  上海有机化学研究所,研究实习员

学术任职、荣誉与获奖:

       主持科技部新药创制重大专项、基金委重点/杰青/面上、中科院战略先导A/前沿重点、上海市重大/重点等项目近30项。其中:(1)通过活性基团再定位技术设计了结构新颖的高活性的PARP1抑制剂1类新药希明哌瑞,获得卫生部优先评审品种推荐及中国药监局颁发的新药临床实验批件,目前正在进行临床Ib/IIa期试验;(2)基于同步靶向肿瘤血管生成及肿瘤微环境策略,设计获得药效显著的1类新药盐酸希美替尼,已获国家药监局临床试验批件,目前正在进行临床I期试验;(3)研发了安全性高对血液瘤药效显著的BTK抑制剂,正在进行系统临床前研究;(4)设计合成了靶向cGAS-STING-TBK1通路小分子激活剂,目前作为新型肿瘤免疫治疗候选药物正在进行临床前研究。

       担任上海科技大学兼职教授,南京中医药大学兼职教授,中国抗癌协会抗癌药物专委会委员,上海药学会药物化学专委会委员;中国药学会药物化学专委会委员,中国药学会高级会员全国卫管理协会精准医疗分会副会长、靶向药物专委会主任委员。

  • 2019:上海市“优秀发明”金奖

  • 2019:中组部第四批“WR计划”

  • 2018:科技部创新人才推进计划“重点领域创新团队”

  • 2018:中国科学院优秀导师奖

  • 2017:中国科学院朱李月华优秀教师奖

  • 2016:上海市优秀学科带头人

  • 2013:明治乳业生物化学学者奖

  • 2013:药明康德生物化学学者奖

  • 2012:“中国侨届贡献奖”-创新人才奖

  • 2011:国家杰出青年基金

  • 2010:中科院“BR计划”终期评估优秀奖

  • 2010:Eli Lilly 亚洲优秀导师奖

  • 2009:上海市“浦江人才”优秀

  • 2007:中科院“BR计划”择优支持

  • 2004:哈佛医学院 Alfred Pope Award for Young Investigator

  • 2004:哈佛医学院McLean 分院 Adam Corneel Young Investigator Fellowship Award Harvard Medical School - McLean Hospital

代表性学术成果

  • Song, Z.; Wang, X.; Zhang, Y.; Gu, W.; Shen, A.; Ding, C.; Li, H.; Xiao, R.; Geng, M.; Xie, Z.;* Zhang, A.* Structure-activity relationship study of amidobenzimidazole analogues leading to potent and systemically administrable STING agonists. J. Med. Chem. 2021, 64, 1649-1669.

  • Liu, X.; Zhang, Y.; Li, Y.; Wang, J.; Huang, W.; Zhao, Z.; Ding, C.; Liu, H.;* Tan, W.;* Zhang, A.* Development of Hedgehog pathway inhibitors by epigenetically targeting GLI through BET bromodomain for the treatment of Medulloblastoma. Acta Pharm. Sin. B, 2021, 11, 488-504..

  • Liu X., Ding C., Tan W.*, Zhang A.* Medulloblastoma: “molecular understanding, treatment evolution, and new developments.” Pharmacol Ther. 2020, 210:107516.

  • Ding C., Chen H., Liang B., Jiao M., Liang G.*, Zhang A.* “Biomimetic synthesis of the natural product salviadione and its hybrids: discovery of tissue-specific anti-inflammatory agents for acute lung injury.” Chem. Sci. 2019, 10, 4667-4672.

  • Ding, C.; Song, Z.; Shen, A.; Chen, T.; Zhang, A.* Small molecules targeting the innate immune cGAS‒STING‒TBK1 signaling pathway. Acta Pharm. Sin. B, 2020, 10 (12), 2272-2298.

  • Xue Y., Song P., Song Z., Wang A., Tong L., Geng M., Ding J., Liu Q., Sun L.*, Xie H.*, Zhang A.* “Discovery of 4,7-diamino-5-(4-phenoxyphenyl) -6-methylene-pyrimido[5,4-b]pyrrolizines as novel Bruton's tyrosine kinase (BTK) inhibitors.” J. Med. Chem. 2018, 61, 4608-4627.

  • Wang D., Yang Z., Wang C.*, Zhang A.*, Uchiyama M.* “From aniline to aryl ether: a facile, efficient and versatile synthetic protocol employing mild conditions.” Angew Chem. Int. Ed. 2018, 57, 3641-3645.

  • Ding C., Tian Q., Li J., Jiao M., Song S., Wang Y.*, Miao Z.*, Zhang A.* “Structural modification of natural product tanshinone I leading to discovery of novel nitrogen-enriched derivatives with enhanced anticancer profile and improved drug-like properties.” J. Med. Chem. 2018, 61, 760-776.

  • Liu G., Yang J., Wang J., Liu X., Huang W., Geng, Y., Tan W.*, Zhang A.* “Discovery of novel macrocyclic hedgehog pathway inhibitors acting by suppressing the Gli-mediated transcription.” J. Med. Chem. 2017, 60, 8218-8245.

  • Liu G., Xue D., Yang J., Wang J., Liu X., Huang W., Li J., Long Y.*, Tan W.*, Zhang A.* “Design, synthesis and pharmacological evaluation of 2-(2,5-dimethyl- 5,6,7,8-tetrahydroquinolin -8-yl)-N-aryl propanamides as novel smoothened (Smo) antagonists.” J. Med. Chem. 2016, 59, 11050-11068.

  • Wang Y., Wang P., Wang Y., Yang G., Zhang A.*, Miao Z.* “An update on poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors: opportunities and challenges in cancer therapy.” J. Med. Chem. 2016, 59, 9575-9598.

  • Fan Z., Ni J., Zhang A.* “Meta-selective CAr-H nitration of arenes through a Ru3(CO)12-catalyzed ortho-metalation strategy.” J. Am. Chem. Soc. 2016, 138, 8470-8475.

  • Wang M., Shen A., Zhang C., Song Z., Ai J., Liu H., Sun L.*, Ding J., Geng M.*, Zhang A.* “Development of heat shock protein (Hsp90) inhibitors to combat resistance to tyrosine kinase inhibitors through Hsp90-kinase interactions.” J. Med. Chem. 2016, 59, 5563-5586.

  • Fan Z., Shu S., Ni J., Yao Q., Zhang A.* “Ligand-promoted Pd(II)-catalyzed functionalization of unactivated C(sp3)−H bond: regio- and stereoselective synthesis of arylated rimantadine derivatives.” ACS Catalysis, 2016, 6, 769-774.

  • Wei M., Wang X., Song Z., Jiao M., Ding J., Meng L.*, Zhang A.* “Targeting PI3Kδ: emerging therapy for chronic lymphocytic leukemia and beyond.” Med. Res. Rev. 2015, 35,720-752.

  • Song Z., Yang Y., Liu Z., Peng X., Guo J., Yang X., Wu K., Ai J.*, Ding J., Geng M.*, Zhang A.* “Discovery of novel 2,4-diarylaminopyrimidine analogues (DAAPalogues) showing potent inhibitory activities against both wild-type and mutant ALK kinases.” J. Med. Chem. 2015, 58, 197-211.

  • Ye N., Neumeyer J. L., Baldessarini R. J., Zhen X., Zhang A.* “Recent progress in the development of dopamine receptor subtype compounds: potential therapeutic agents for neurological and neuropsychiatric disorders.” Chem. Rev. 2013, 113, PR123-PR178.

  • Ye N., Chen C., Chen T., Song Z., He J., Huan X., Song S., Liu Q., Chen Y., Ding J., Xu Y.*, Miao Z.*, Zhang A.* “Design, synthesis and biological evaluation of a series of benzo[de][1,7] naphthyridin-7(8H)-ones bearing a functionalized longer chain appendage as novel PARP1 inhibitors.” J. Med. Chem. 2013, 56, 2885-2903.

  • Zhang H., Ye N., Zhou S., Guo L., Zheng L., Liu Z., Gao B., Zhen X.*, Zhang A.* “Identification of N-propylnoraporphin-11-yl 5-(1,2-Dithiolan-3-yl)pentanoate as a new anti-parkinson's agent possessing a dopamine D2 and serotonin 5-HT1A dual-agonist profile.” J. Med. Chem. 2011, 54, 4324-4338.

  • Wang Y., Ai J., Wang Y., Chen Y., Wang L., Liu G., Geng M.*, Zhang A.* “Synthesis and c-Met kinase inhibition of 3,5-di- and 3,5,7-tri- substituted quinolines: identification of 3-(4-acetylpiperazin-1-yl)- 5-(3-nitrobenzylamino)- 7- (trifluoromethyl)quinoline as a novel anticancer agent.” J. Med. Chem. 2011, 54, 2127-2142.