新萄京网址33522

 

师资队伍

师资队伍
师资队伍

丁春勇

研究员

 

电话:(021)34204016
传真:(021)34204016
邮箱:chunding@sjtu.edu.cn
主页:地址:上海市东川路800号新萄京网址335226号楼502室 主页:药物化学生物学及新药发现前沿研究实验室(Research Laboratory of Medicinal Chemical Biology & Frontiers on Drug Discovery, RLMCBFDD)

学历及经历
2001.9‒2005.6 本科, 中国药科大学新萄京网址33522
2005.9‒2010.6 博士,中国药科大学新萄京网址33522(导师:姚其正教授)
2010.7‒2013.10 博士后,美国德州大学医学分部(导师:Jia Zhou 教授)
2013.11‒2014.9 助理研究员,中科院上海药物研究所
2014.10‒2019.9 副研究员,硕士研究生导师,中科院上海药物研究所
2019.10‒2020.2 研究员,硕士研究生导师,中科院上海药物研究所
2020.3‒至今 研究员,新萄京网址33522
荣誉及奖励
2013 全国药物化学会议-青年优秀论文奖
2014 上海市浦江人才计划
2019 中国精准医疗大会-青年学者创新成果奖(第一名)
2019 赛诺菲-中科院上海生科院优秀青年人才基金奖励
社会及科技协会兼职
 中国药学会会员,中国化学会会员,中国生物化学与分子生物学会会员
 Current Topics in Medicinal Chemistry杂志Executive Guest Editors (执行客座编辑)
致力于基于我国特色天然产物的创新药物发现及相关基础研究。通过天然产物全合成及其结构优化、化学蛋白质组学、生物信息学和分子影像等多学科手段,系统构建了基于天然产物的药物化学生物学研究体系,揭示多个天然产物作用靶标与机制,获得抗急性肺损伤和肿瘤免疫治疗等多个原创性药物候选化合物。2个1类候选新药处于临床前研究,其中,基于肿瘤免疫治疗的1类候选新药已实现成果转让。主持国家基金委青年、面上项目、中科院先导专项子课题及上海市科委等5项科研项目。发表第一/通讯作者SCI论文28篇,包括Chem Sci, J Med Chem, Cancer Res,Anal Chem, Org Lett, Cancer Lett和ChemComm等JCR 1区期刊18篇。入选上海市浦江人才计划,获赛诺菲-上海生科院优秀青年人才奖和中国精准医疗大会-青年学者创新成果展示。
1. 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, https:// doi.org/10.1016/j.apsb.2020.03.001.
2. Xiao R.#, Ding C.#, Zhu H., Liu X., Gao J., Liu Q., Lu D., Zhang N.*, Zhang A.*, Zhou H.* “Suppression of asparagine synthetase enhances the antitumor potency of ART and artemalogue SOMCL-14-221 in non-small cell lung cancer.” Cancer Lett. 2020, 475, 22-33.
3. Dang Y., Wang F., Li L., Lai Y., Xu Z.*, Xiong Z., Zhang A., Tian Y., Ding C.*, Zhang W.*. “An activatable near-infrared fluorescent probe for methylglyoxal imaging in Alzheimer's disease mice.” Chem. Commun. 2020, 56, 707-710.
4. Mao X., Ni J., Xu B.*. Ding C.*. “K2S2O8-promoted direct thiocyanation of pyrazolin-5-ones with ammonium thiocyanate at room temperature.” Org. Chem. Front. 2020, 7, 350-354.
5. Ding C.*,#, Wang F.#, Dang Y.#, Xu Z.*, Li L., Lai Y., Yu H., Luo Y., Huang R., Zhang A., Zhang W.*. “Imaging tumorous methylglyoxal by an activatable near-infrared fluorescent probe for monitoring glyoxalase 1 activity.” Anal. Chem. 2019, 91, 15577-15584.
6. 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.
7. Ding C. #, Tian Q. #, Li J., Jiao M., Song S., Wang Y.*, Miao Z.-H.*, 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.
8. Wang F., Yu S., Xu Z.*, Li L., Dang Y., Xu X., Luo Y., Cheng Z., Yu H., Zhang W., Zhang A., Ding C.*. “Acid-promoted D-A-D type far-red fluorescent probe with high photostability for lysosomal nitric oxide imaging.” Anal Chem. 2018, 90, 7953-7962.
9. Li R.,# Ding C.,# Zhang J.,# Xie M., Park D., Ding Y., Chen G., Zhang G., Gilbert-Ross M., Zhou W., Marcus A. I., Sun S. Y., Chen Z. G., Sica G. L., Ramalingam S. S., Magis A. T., Fu H., Khuri F. R., Curran W. J., Owonikoko T. K., Shin D. M., Zhou J.*, Deng X.* “Modulation of bax and mTOR for cancer therapeutics.” Cancer Res. 2017, 77, 3001-3012.
10. Tian Q.#, Ding C.#, Song S., Wang Y.*, Zhang A.*, Miao Z.*. “New tanshinone I derivatives S222 and S439 similarly inhibit topoisomerase I/II but reveal different p53-dependency in inducing G2/M arrest and apoptosis.” Biochem. Pharmacol. 2018, 154, 255-264.
11. Li J., Xue Y., Fan Z., Ding C. *, Zhang A.* “Difluorination of furonaphthoquinones.” J. Org. Chem. 2017, 82, 7388-7393.
12. Ding C.#, Li J.#, Jiao M., Zhang A.*. “Catalyst-free sp3 C-H acyloxylation: regioselective synthesis of 1-acyloxy derivatives of the natural product tanshinone IIA.” J. Nat. Prod. 2016, 79, 2514-2520.
13. Liu G., Song S., Shu S., Miao Z., Zhang A., Ding C.* “Novel spirobicyclic artemisinin analogues (artemalogues): synthesis and antitumor activities.” Eur. J. Med. Chem. 2015, 103, 17-28.
14. Ding C., Zhang Y., Chen H., Yang Z., Wild C., Ye N., Ester C. D., Xiong A., White M. A., Shen Q.*, Zhou J.* “Oridonin ring a-based diverse constructions of enone functionality: identification of dienone analogues effective for highly aggressive breast cancer by inducing apoptosis.” J Med Chem. 2013, 56, 8814-8825.
15. Ding C., Zhang Y., Chen H., Wild C., Wang T., White M. A., Shen Q., Zhou J.* “Overcoming synthetic challenges of oridonin a-ring structural diversification: regio- and stereoselective installation of azides and 1,2,3-triazoles at the C-1, C-2, or C-3 position.” Org. Lett. 2013, 15, 3718-3721.
16. Ding C., Zhang Y., Chen H., Chu L., Yang Z., Wild C., Liu H., Shen Q.*, Zhou J.* “Novel nitrogen-enriched oridonin analogs with thiazole-fused a-ring: orotecting group-free synthesis, enhanced anticancer profile, and improved aqueous solubility.” J. Med. Chem. 2013, 56, 5048-5058.
17. Ding C., Bremer N. M., Smith T. D., Seitz P. K., Anastasio N. C., Cunningham K. A., Zhou J.* “Exploration of synthetic approaches and pharmacological evaluation of PNU-69176E and its stereoisomer as 5-HT2C receptor allosteric modulators.” ACS Chem. Neurosci. 2012, 3, 538-545.
18. Ding C., Tu S., Yao Q.*, Li F., Wang Y., Hu W., Zhang A.*. “One-pot three-step synthesis of naphtho[2,3-a]carbazole-5,13-diones using tandem radical alkylation-cyclization-aromatization reaction sequence.” Adv. Synth. Catal. 2010, 352, 847-853.
19. Ding C., Tu S., Wang Y., Hu W., Meng L., Yao Q.*, Zhang A.* “Synthesis study on Marmycin A: preparation of the C3’-desmethyl analogues.” J. Org. Chem. 2009, 74, 6111-6119.
20. Wang F., Yang H., Yu S., Xue Y., Fan Z., Liang G., Geng M., Zhang A., Ding C.* “Total synthesis of (±)-tanshinol B, tanshinone I, and (±)-tanshindiol B and C.” Org. Biomol. Chem. 2018, 16, 3376-3381.
21. Jiao M., Liu G., Xue, Y., Ding C.* “Computational drug repositioning for cancer therapeutics.” Curr. Top. Med. Chem. 2015, 15, 767-775.
主要研究成果:
(1)建立“一锅多步”串联环化反应,实现Salviadione的首次仿生合成,巧妙运用仿生杂合策略,获得肺组织特异性分布的抗急性肺损伤候选药物,并揭示潜在作用靶标与机制,为开发安全、有效的急性肺损伤治疗药物提供新结构和新靶标机制(Chem Sci 2019)。
(2)突破丹参酮结构改造的传统思路,首次实现四环骨架的氮杂化修饰,获得成药性和药效显著改善的全新结构衍生物(J Med Chem 2018);并揭示其直接作用靶标和多通路协同的抗肿瘤机制,推动丹参酮类天然产物在抗肿瘤领域的研究与开发(Biochem Pharmacol 2018)。
(3)通过螺环/稠环化策略,获得抗肿瘤活性显著提高的全新青蒿素衍生物(Eur J Med Chem 2015);利用定量比较蛋白组学等手段,阐明内质网应激诱导的抗肿瘤作用机制,并首次揭示抗肿瘤活性与关键节点蛋白ASNS的相关性,为与ASNS抑制剂的联合用药提供重要依据(Cancer Lett 2020)。
(4)发展了一系列立体和区域选择性化学修饰方法,实现对复杂结构天然产物冬凌草甲素的精准结构改造,为基于该天然产物的药物化学生物学研究开辟新的化学空间(J Med Chem 2013, 56, 5048; J Med Chem 2013, 56, 8814; Org Lett 2013)。
(5)干扰素刺激因子STING是目前肿瘤免疫治疗的前沿热点,但尚无能够口服的小分子激动剂进入临床。通过对天然产物衍生物库筛选和基于靶标结构的药物设计,获得口服有效的非环核苷STING小分子激动剂,并实现成果转让,该候选药物有望通过激活机体天然免疫实现肿瘤的治疗,克服目前PD1/PDL1抗体仅对部分“热”肿瘤有效的局限(Acta Pharm Sin B 2020)。
(6)首次基于D-A-D型苯并噻二唑光电材料结构骨架,构建一系列靶向疾病分子标志物的智能响应型荧光探针,为基于分子功能可视化的肿瘤、炎症和老年痴呆等疾病的诊断、药物作用机制和疗效评估及预后判定奠定基础。主要包括:
a. 构建溶酶体靶向的比率型远红外NO探针,为研究溶酶体NO与炎症等疾病的关系及抗炎药物的疗效监控提供可视化工具 (Anal Chem 2018)。
b. 发展首个体内外检测肿瘤MGO的高性能近红外荧光探针,不仅能原位荧光检测GLO1代谢酶活性,还可对GLO1抑制剂进行可视化筛选和疗效评估(Anal Chem 2019),为阐明肿瘤糖酵解调控机制奠定基础。
c. 利用MGO近红外荧光探针,首次从分子影像学角度证实AD小鼠脑中MGO含量高于野生型,为阐明MGO在AD发生发展中的角色提供影像学证据 (ChemComm 2020)。
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新萄京网址33522
地址:上海市东川路800号
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