姜标课题组介绍
姜标 ( Co-PI：陈红莉 ) |
|
姜标，特聘教授 通讯地址：人字楼A407 电子邮件：jiangbiao@shanghaitech.edu.cn chenhl@shanghaitech.edu.cn 个人简历： 国际欧亚科学院院士；中科院曼谷创新合作中心主任；上海标新医药生物创始人；曾任中国科学院上海有机化学研究所所长、中国科学院上海高等研究院副院长、上海科技大学免疫化学研究所执行所长。曾获得2项国家科技进步二等奖、2项求是奖、2项中国产学研奖、联合国环境规划署环境保护杰出成就奖、中国科学院科学杰出贡献奖等40多项奖励；为我国履行《关于汞的水俣公约》、《蒙德利尔议定书》和《巴黎气候条约》做出积极贡献。发表学术论文300余篇，申请专利200余项；欧美德日等国专利10余项，近60多项专利转让或授权企业转化。作为副主编出版《中药天然产物大全》（12卷，约3000万字）。
|
抗体药物偶联物、蛋白降解技术 |
本课题组致力于创新药物研究，是一个集化学、生物学及药学多学科交叉的实验室，侧重于抗体药物偶联物(Antibody-Drug Conjugates)和蛋白降解技术(Protelysis Targeting Drug) 核心技术的建立，聚焦于尖端药物的研究和开发。 |
(1) Yu, X.; Sun, Z.; Liu, J.; Huangfu, S.; Cheng, Q.; Chen, J.; Yang, X.; Jiang, B.; Chen, H. Deuterium substitution at the intolerable site as a strategy to mitigate the toxicity of camptothecin derivatives. European Journal of Medicinal Chemistry 2025, 296, 117877. DOI: 10.1016/j.ejmech.2025.117877. (2) Wu, T.; Zhou, H.-X.; Tian, J.; Zhou, R.; Huangfu, S.; Jin, B.-K.; Sablina, A.; Zhou, F.; Chen, H.; Tang, S.; et al. Enrichable cross-linkers for mapping direct protein interactions. Genome Biology 2025, 26 (1). DOI: 10.1186/s13059-025-03669-5. (3) Wei, D.; Wang, H.; Huangfu, S.; Qi, C.; Jiang, Y.; Yu, X.; Jiang, B.; Chen, H. Fine-tuning phenoxy silyl scaffolds for the development of glutathione-responsive prodrugs and antibody–drug conjugates. Bioorganic & Medicinal Chemistry 2025, 120, 118088. DOI: 10.1016/j.bmc.2025.118088. (4) Wang, H.; Huangfu, S.; Wei, D.; Sun, Z.; Wu, Y.; Yu, X.; Jiang, B.; Chen, H. Triptolide-based cleavable antibody-drug conjugates for pancreatic cancer. European Journal of Medicinal Chemistry 2025, 295, 117798. DOI: 10.1016/j.ejmech.2025.117798. (5) Qu, X.; Ou, H.; Wu, Y.; Jiang, B.; Song, X. Amiloride synergizes with EGFR PROTACs and inhibitors to overcome therapeutic resistance in NSCLC. Bioorganic Chemistry 2025, 163, 108641. DOI: 10.1016/j.bioorg.2025.108641. (6) Li, T.; Yu, X.; Wan, X.; Liu, J.; Zheng, J.; Sun, Z.; Zhao, Y.; Chen, J.; Chen, H.; Yang, Y.; et al. Exploiting synthetic lethality in PDAC with antibody drug conjugates and ATR inhibition. European Journal of Medicinal Chemistry 2025, 286, 117305. DOI: 10.1016/j.ejmech.2025.117305. (7) Li, D.; Shen, S.; Liu, C.; Guo, T.; Liu, Y.; Pan, P.; Zhao, X.; Ma, Y.; Li, L.; Huang, S.; et al. Discovery of novel and highly potent anticancer agents enabled by selenium scanning of noscapine. European Journal of Medicinal Chemistry 2025, 293, 117714. DOI: 10.1016/j.ejmech.2025.117714. (8) Zhu, X.; Li, Y.; Liu, H.; Wang, Y.; Sun, R.; Jiang, Z.; Hou, C.; Hou, X.; Huang, S.; Zhang, H.; et al. NAMPT-targeting PROTAC and nicotinic acid co-administration elicit safe and robust anti-tumor efficacy in NAPRT-deficient pan-cancers. Cell Chemical Biology 2024, 31 (6), 1203-1218.e1217. DOI: 10.1016/j.chembiol.2024.05.007. (9) Zhang, X.; Tao, Y.; Xu, Z.; Jiang, B.; Yang, X.; Huang, T.; Tan, W. Sorafenib and SIAIS361034, a novel PROTAC degrader of BCL-xL, display synergistic antitumor effects on hepatocellular carcinoma with minimal hepatotoxicity. Biochemical Pharmacology 2024, 230. DOI: 10.1016/j.bcp.2024.116542. (10) Yang, J.; Wu, Y.; Zhu, Q.; Qu, X.; Ou, H.; Liu, H.; Wei, Y.; Ge, D.; Lu, C.; Jiang, B.; et al. Discovery of a first-in-class protein degrader for the c-ros oncogene 1 (ROS1). Bioorganic Chemistry 2024, 150. DOI: 10.1016/j.bioorg.2024.107590. (11) Luo, C.-H.; Hu, L.-H.; Liu, J.-Y.; Xia, L.; Zhou, L.; Sun, R.-H.; Lin, C.-C.; Qiu, X.; Jiang, B.; Yang, M.-Y.; et al. CDK9 recruits HUWE1 to degrade RARα and offers therapeutic opportunities for cutaneous T-cell lymphoma. Nature Communications 2024, 15 (1). DOI: 10.1038/s41467-024-54354-3. (12) Huangfu, S.; Yu, X.; Sun, Z.; Jiang, B.; Chen, H. Chemical reagents for the enrichment of modified peptides in MS-based identification. Chemical Communications 2024, 60 (12), 1509. DOI: 10.1039/d3cc05260e. (13) Wei, D.; Mao, Y. R.; Wang, H. H.; Qu, S. Q.; Chen, J. K.; Li, J. S.; Jiang, B.; Chen, H. L. A mild phenoxysilyl linker for self-immolative release of antibody-drug conjugates. Chinese Chemical Letters 2023, 34 (5), 108091. DOI: 10.1016/j.cclet.2022.108091. (14) Wei, D.; Jiang, Y.; Mao, Y.; Xu, Z.; Chen, J.; Gao, X.; Li, J.; Jiang, B.; Chen, H. Phenyldivinylsulfonamides for the construction of antibody–drug conjugates with controlled four payloads. Bioorganic Chemistry 2023, 134, 106463. DOI: 10.1016/j.bioorg.2023.106463. (15) Wang, H.; Yang, Q.; Liu, X.; Xu, Z.; Shao, M.; Li, D.; Duan, Y.; Tang, J.; Yu, X.; Zhang, Y.; et al. Structure-based discovery of dual pathway inhibitors for SARS-CoV-2 entry. Nature Communications 2023, 14 (1). DOI: 10.1038/s41467-023-42527-5. (16) Mao, Y. R.; Wei, D.; Fu, F. Q.; Wang, H. H.; Sun, Z. Y.; Huang, Z. Y.; Wang, Y.; Zhang, G. B.; Zhang, X. G.; Jiang, B.; et al. Development of a MMAE-based antibody-drug conjugate targeting B7-H3 for glioblastoma. European Journal of Medicinal Chemistry 2023, 257, 115489. DOI: 10.1016/j.ejmech.2023.115489. (17) Liu, L.; Sun, R.; Liu, H.; Ren, C.; Zhou, Y.; Qiu, X.; Kong, Y.; Jiang, B.; Yang, X. Design, synthesis and biological evaluation of novel quinazolinone derivatives as CRBN E3 ligase modulators. European Journal of Medicinal Chemistry 2023, 247, 115016. DOI: 10.1016/j.ejmech.2022.115016. (18) Liu, C.; Ding, X.; Li, G.; Zhang, Y.; Shao, Y.; Liu, L.; Zhang, W.; Ma, Y.; Guan, W.; Wang, L.; et al. Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma. iScience 2023, 26 (8), 107369. DOI: 10.1016/j.isci.2023.107369. (19) Li, M.; Zhao, H.; Chen, S.; liu, S.; Yan, L.; Hou, C.; Jiang, B. Reengineering of the carbon-to-acetylene process featuring negative carbon emission. Green Chemistry 2023, 25 (21), 8584-8592. DOI: 10.1039/d3gc01775c. (20) Zhu, X.; Liu, H.; Chen, L.; Wu, C.; Liu, X.; Cang, Y.; Jiang, B.; Yang, X.; Fan, G. Addressing the Enzyme-independent tumor-promoting function of NAMPT via PROTAC-mediated degradation. Cell Chemical Biology 2022, 29(11):1616-1629.e12. DOI: 10.1016/j.chembiol.2022.10.007. (21) Zhang, S.; Chen, Y.; Xu, Z.; Yang, J.; Sun, R.; Wang, J.; Sun, Y.; Jiang, B.; Yang, X.; Tan, W. The PROTAC selectively degrading Bcl-x(L) represents a novel Hedgehog pathway inhibitor with capacity of combating resistance to Smoothened inhibitors while sparing bone growth. Theranostics 2022, 12 (17), 7476-7490. DOI: 10.7150/thno.75421. (22) Yang, Y.; Lu, W.; Ning, M.; Zhou, X.; Wan, X.; Mi, Q.; Yang, X.; Zhang, D.; Zhang, Y.; Jiang, B.; et al. A functional SNP rs895819 on pre-miR-27a is associated with bipolar disorder by targeting NCAM1. Commun Biol 2022, 5 (1), 309. DOI: 10.1038/s42003-022-03263-6. (23) Xu, Z.; Wang, H.; Liu, H.; Chen, H.; Jiang, B. Synthesis and Evaluation of Reactive Oxygen Species Sensitive Prodrugs of a NAMPT Inhibitor FK866. Molecules 2022, 28 (1), 169. DOI: 10.3390/molecules28010169 From NLM Medline. (24) Liu, H.; Ren, C.; Sun, R.; Wang, H.; Zhan, Y.; Yang, X.; Jiang, B.; Chen, H. Reactive oxygen species-responsive Pre-PROTAC for tumor-specific protein degradation. Chemical Communications 2022, 58 (72), 10072. DOI: 10.1039/d2cc03367d. (25) Liu, H.; Mi, Q.; Ding, X.; Lin, C.; Liu, L.; Ren, C.; Shen, S.; Shao, Y.; Chen, J.; Zhou, Y.; et al. Discovery and characterization of novel potent BCR-ABL degraders by conjugating allosteric inhibitor. Eur J Med Chem 2022, 244, 114810. DOI: 10.1016/j.ejmech.2022.114810. (26) Zhang, Y.; Luo, T.; Ding, X.; Chang, Y.; Liu, C.; Zhang, Y.; Hao, S.; Yin, Q.; Jiang, B. Inhibition of mitochondrial complex III induces differentiation in acute myeloid leukemia. Biochem Biophys Res Commun 2021, 547, 162-168. DOI: 10.1016/j.bbrc.2021.02.027. (27) Wei, D.; Mao, Y. R.; Xu, Z. L.; Chen, J. K.; Li, J. S.; Jiang, B.; Chen, H. L. Site-specific construction of triptolide-based antibody-drug conjugates. Bioorganic & Medicinal Chemistry 2021, 51, 116497. DOI: 10.1016/j.bmc.2021.116497. (28) Ren, C.; Sun, N.; Liu, H.; Kong, Y.; Sun, R.; Qiu, X.; Chen, J.; Li, Y.; Zhang, J.; Zhou, Y.; et al. Discovery of a Brigatinib Degrader SIAIS164018 with Destroying Metastasis-Related Oncoproteins and a Reshuffling Kinome Profile. J Med Chem 2021, 64 (13), 9152-9165. DOI: 10.1021/acs.jmedchem.1c00373. (29) Ren, C.; Sun, N.; Kong, Y.; Qu, X.; Liu, H.; Zhong, H.; Song, X.; Yang, X.; Jiang, B. Structure-based discovery of SIAIS001 as an oral bioavailability ALK degrader constructed from Alectinib. Eur J Med Chem 2021, 217, 113335. DOI: 10.1016/j.ejmech.2021.113335. (30) Qu, X.; Liu, H.; Song, X.; Sun, N.; Zhong, H.; Qiu, X.; Yang, X.; Jiang, B. Effective degradation of EGFRL858R+T790M mutant proteins by CRBN-based PROTACs through both proteosome and autophagy/lysosome degradation systems. European Journal of Medicinal Chemistry 2021, 218, 113328. DOI: 10.1016/j.ejmech.2021.113328. (31) Liu, H.; Ding, X.; Liu, L.; Mi, Q.; Zhao, Q.; Shao, Y.; Ren, C.; Chen, J.; Kong, Y.; Qiu, X.; et al. Discovery of novel BCR-ABL PROTACs based on the cereblon E3 ligase design, synthesis, and biological evaluation. Eur J Med Chem 2021, 223, 113645. DOI: 10.1016/j.ejmech.2021.113645. (32) Huang, R.; Zhu, W.; Xu, Z.; Chen, J.; Jiang, B.; Chen, H.; Chen, W. Accurate Retention Time Prediction Based on Monolinked Peptide Information to Confidently Identify Cross-Linked Peptides. Journal of the American Society for Mass Spectrometry 2021, 32 (9), 2410. DOI: 10.1021/jasms.1c00120. (33) Huang, R.; Sheng, Y.; Xu, Z. L.; Wei, D.; Song, X. L.; Jiang, B.; Chen, H. L. Combretastatin A4-derived payloads for antibody-drug conjugates. European Journal of Medicinal Chemistry 2021, 216, 113355. DOI: 10.1016/j.ejmech.2021.113355. (34) Sun, N.; Ren, C.; Kong, Y.; Zhong, H.; Chen, J.; Li, Y.; Zhang, J.; Zhou, Y.; Qiu, X.; Lin, H.; et al. Development of a Brigatinib degrader (SIAIS117) as a potential treatment for ALK positive cancer resistance. Eur J Med Chem 2020, 193, 112190. DOI: 10.1016/j.ejmech.2020.112190. (35) Liu, H.; Sun, R.; Ren, C.; Qiu, X.; Yang, X.; Jiang, B. Construction of an IMiD-based azide library as a kit for PROTAC research. Org Biomol Chem 2020, 19(1):166-170. DOI: 10.1039/d0ob02120b. (36) Huang, R.; Sheng, Y.; Wei, D.; Yu, J. H.; Chen, H. L.; Jiang, B. Bis(vinylsulfonyl)piperazines as efficient linkers for highly homogeneous antibody-drug conjugates. European Journal of Medicinal Chemistry 2020, 190, 112080. DOI: 10.1016/j.ejmech.2020.112080. (37) Huang, R.; Sheng, Y.; Wei, D.; Lu, W.; Xu, Z.; Chen, H.; Jiang, B. Divinylsulfonamides enable the construction of homogeneous antibody–drug conjugates. Bioorganic & Medicinal Chemistry 2020, 28 (23), 115793. DOI: 10.1016/j.bmc.2020.115793. (38) Huang, R.; Gao, X.; Xu, Z.; Zhu, W.; Wei, D.; Jiang, B.; Chen, H.; Chen, W. Decision Tree Searching Strategy to Boost the Identification of Cross-Linked Peptides. Analytical Chemistry 2020, 92 (20), 13702. DOI: 10.1021/acs.analchem.0c00452. (39) Zhao, Q.; Ren, C.; Liu, L.; Chen, J.; Shao, Y.; Sun, N.; Sun, R.; Kong, Y.; Ding, X.; Zhang, X.; et al. Discovery of SIAIS178 as an Effective BCR-ABL Degrader by Recruiting Von Hippel–Lindau (VHL) E3 Ubiquitin Ligase. Journal of Medicinal Chemistry 2019, 62 (20), 9281-9298. DOI: 10.1021/acs.jmedchem.9b01264. (40) Qiu, X.; Sun, N.; Kong, Y.; Li, Y.; Yang, X.; Jiang, B. Chemoselective Synthesis of Lenalidomide-Based PROTAC Library Using Alkylation Reaction. Org Lett 2019, 21 (10), 3838-3841. DOI: 10.1021/acs.orglett.9b01326. (41) Huang, R.; Zhu, W.; Wu, Y.; Chen, J.; Yu, J.; Jiang, B.; Chen, H.; Chen, W. A novel mass spectrometry-cleavable, phosphate-based enrichable and multi-targeting protein cross-linker. Chemical Science 2019, 10 (26), 6443. DOI: 10.1039/c9sc00893d. (42) Huang, R.; Li, Z.; Yu, J.; Chen, H.; Jiang, B. H2O-Regulated Chemoselectivity in Oxa- Versus Aza-Michael Reactions. Organic Letters 2019, 21 (11), 4159-4162. DOI: 10.1021/acs.orglett.9b01342.
|
