师资队伍

沈玉道

长聘教轨副教授

 

邮箱:yudao.shen@sjtu.edu.cn
主页:https://pharm.sjtu.edu.cn/szdy/4162.html

沈玉道 博士,副教授(Tenure Track)、博士生导师、独立课题组长(PI)。通过“2021上海交通大学人才引进绿色通道”加入上海交通大学药学院,并先后入选“2021上海市海外高层次人才计划(青年)”和“2022国家海外高层次人才计划(青年)”。2007/9-2013/7 中国科学院上海有机化学研究所 有机化学 博士 导师: 李超忠研究员;2013/10-2014/8 北卡罗莱纳大学教堂山分校(University of North Carolina at Chapel Hill) 药物化学 博士后 导师: Jian Jin教授;2014/9-2019/12 西奈山伊坎医学院(Icahn School of Medicine at Mount Sinai) 药物化学 博士后 导师: Jian Jin教授;2020/1-2022/4 西奈山伊坎医学院(Icahn School of Medicine at Mount Sinai) 药物化学 讲师 导师:Jian Jin教授;2022/6-至今 上海交通大学药学院 药物化学 。
结合有机合成和药理学技术:1. 围绕表观遗传肿瘤靶标,通过发展抑制剂和降解剂,研发临床抗肿瘤药物;2. 围绕G蛋白偶联受体,通过发展选择性激动剂,研发神经退行性和精神性疾病方面的临床药物。
热忱欢迎有机化学、药物化学和药理学相关专业的博士后、博士和硕士研究生、本科生的加入!
发表论文:
1. Dale, B.; Anderson, C.; Park, K-S.; Kaniskan, H.; Ma, A.; Shen, Y.; Zhang, C.; Xie, L.; Yu. X.; Jin, J. Targeting Triple-Negative Breast Cancer by a Novel Proteolysis Targeting Chimera Degrader of Enhancer of Zeste Homolog 2. ACS Pharmacol. Transl. Sci. 2022, in press.
2. Yu, X.; Cheng, M.; Lu, K.; Shen, Y.; Zhong, Y.; Liu, J.; Xiong, Y.; Jin, J. Exploring Degradation of Mutant and Wild-Type Epidermal Growth Factor Receptors Induced by Proteolysis-Targeting Chimeras. J. Med. Chem. 2022, 65, 8416-8443.
3. Wu, Q.; Nie, D. Y.; Ba-Alawi, W.; Ji, Y.; Zhang, Z.; Cruickshank, J.; Haight J.; Ciamponi F. E.; Chen, J.; Duan, S.; Shen, Y.; Liu, J.; Marhon, S. A..; Mehdipour, P.; Szewczyk, M. M.; Dogan-Artun, N.; Chen, W.; Zhang, L. X.; Deblois, G.; Prinos, P.; Massirer, K. B.; Barsyte-Lovejoy, D.; Jin, J.; De Carvalho, D. D.; Haibe-Kains, B.; Wang, X.; Cescon, D. W.; Lupien, M.; Arrowsmith, C. H. PRMT inhibition induces a viral mimicry response in triple-negative breast cancer. Nat. Chem. Biol. 2022, in print.
4. Li, D.; Yu, X.; Kottur, J.; Gong, W.; Zhang, Z.; Storey, A. J.; Tsai, Y. H.; Uryu, H.; Shen, Y.; Byrum, S. D.; Edmondson, R. D.; Mackintosh, S. G.; Cai, L.; Liu, Z.; Aggarwal, A. K.; Tackett, A. J.; Liu, J.; Jin, J.; Wang, G. G. Discovery of a dual WDR5 and Ikaros PROTAC degrader as an anti-cancer therapeutic. Oncogene. 2022, in print.
5. Wang, J.; Yu, X.; Gong, W.; Liu, X.; Park, K.-S.; Ma, A.; Tsai, Y.-H.; Shen, Y.; Onikubo, T.; Pi, W.-C.; Allison, D. F.; Liu, J.; Chen, W-Y.; Cai, L.; Roeder, R. G.; Jin, J.; Wang, G. G. EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis. Nat. Cell. Biol. 2022, 24, 384-399.
6. Yu, X.; Xu, J.; Shen, Y.; Cahuzac, K.; Park, K.; Dale, B.; Liu, J.; Parsons, R.; Jin, J. Discovery of potent, selective, and in vivo efficacious AKT kinase protein degraders via structure-activity relationship studies. J. Med. Chem. 2022, 65, 3644-3666.
7. Yu, X.; Xu, J.; Xie, L.; Wang, L.; Shen, Y.; Cahuzac, K.; Chen, X.; Liu, J.; Parsons, R.; Jin, J. Design, Synthesis and Evaluation of Potent, Selective and Bioavailable AKT Kinase Degraders. J. Med. Chem. 2021, 64, 18054-18081.
8. Yu, X.; Li, D.; Kottur, J.; Shen, Y.; Kim, H. S.; Park, K. S.; et al, Kaniskan, H. Ü.; Cai, L.; Jain, R.; Liu, J.; Aggarwal, A. K.; Wang, G. G.; Jin, J. A Selective WDR5 Degrader Inhibits Acute Myeloid Leukemia in Patient-Derived Mouse Models. Sci. Transl. Med. 2021, 13, eabj1578.
9. Wei, J.; Meng, F.; Park, K.; Yim, H.; Velez, J.; Kumar, P.; Wang, L.; Xie, L.; Chen, H.; Shen, Y.; Teichman, E.; Wang, G.; Chen, X.; Kaniskan, H.; Jin, J. Harnessing the E3 ligase KEAP1 for targeted protein degradation. J. Am. Chem. Soc. 2021, 143, 15073-15083.
10. Shen, Y.; Li, F.; Szewczyk, M. M.; Halabelian, L.; Chau, I.; Eram, M. S.; Dela Sena, C.; Park, K. S.; Meng, F.; Chen, H.; Zeng, H.; McLeod, D.; Zepeda-Velazquez, C. A.; Campbell, R. M.; Mader, M. M.; Watson, B. M.; Schapira, M.; Arrowsmith, C. H.; Al-Awar, R.; Barsyte-Lovejoy, D.; Kaniskan, H. U.; Brown, P. J.; Vedadi, M.; Jin, J. A First-in-class, Highly Selective and Cell-active Allosteric Inhibitor of Protein Arginine Methyltransferase 6 (PRMT6). J. Med. Chem. 2021, 64, 3697-3796. (featured article)
11. Shen, Y.; Szewczyk, M. M.; Eram, M. S.; Smil, D.; Kaniskan, H. Ü.; de Freitas, R. F.; Senisterra, G.; Li, F.; Schapira, M.; Brown, P. J.; Arrowsmith, C. H.; Barsyte-Lovejoy, D.; Liu, J.; Vedadi, M.; Jin, J. Discovery of a Potent, Selective and Cell-active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. J. Med. Chem. 2016, 59, 9124-9139.
12. Liu, J. ; Chen, H.; Liu, Y.; Shen, Y.; Meng, F.; Kaniskan, H. U.; Jin, J.; Wei, W. Cancer selective target degradation by folate-caged PROTACs. J. Am. Chem. Soc. 2021, 143, 7380-7387.
13. Xu, J.; Yu, X.; Martin, T. C.; Bansal, A.; Cheung, K.; Lubin, A.; Stratikopoulos, E.; Cahuzac, K. M.; Wang, L.; Xie, L.; Zhou, R.; Shen, Y.; Wu, X.; Yao, S.; Qiao, R.; Poulikakos, P. I.; Chen, X.; Liu, J.; Jin, J.; Parsons, R. AKT degradation selectively inhibits the growth of PI3K/PTEN pathway mutant cancers with wild-type KRAS and BRAF by destabilizing Aurora kinase B. Cancer Discovery 2021, 11, 3064-3089.
14. Lu, S.; Neef, E.; Thomas, J.; Sabio, E.; Rousseau, B; Gigoux, M.; Knorr, D.; Greenbaurin, B.; Elhanat, Y.; Hogg , S.; Chow, A.; Ghosh, A.; Xie, A.; Zamarin, D.; Cui, D.; Erickson, C.; Singer, M.; Cho, H.; Wang, E.; Lu, B.; Durham, B.; Shah, H.; Chowell, D.; Gabel, A.; Shen, Y.; Liu, J.; Jin, Jian.; Rhodes, M.; Taylor, R.; Molina, H.; Wolchook, J.; Mergoub, T.; Diaz Jr. L.; Abdel-Wahab, O.; Bradley, R. Pharmacologic modulation of RNA splicing enhances anti-tumor immunity. Cell 2021, 184, 4032-4047.
15. Su, H.; Jiang, M.; Senevirathne, C.; Aluri, S.; Zhang, T.; Guo, H.; Xavier-Ferrucio, J.; Jin, S.; Tran, N.; Liu, S.; Sun, C.; Zhu, Y.; Zhao, Q.; Chen, Y.; Cable, L.; Shen, Y.; Liu, J.; Qu, C.; Han, X.; Klug, C.; Bhatia, R.; Chen, Y.; Nimer, S.; Zheng, Y.; Iancu-Rubin, C.; Jin, J.; Deng, H.; Krause, C.; Xiang, J.; Verma, A.; Luo, M.; Zhao, X. Methylation of Dual Specificity Phosphatase 4 Controls Cell Differentiation. Cell Reports 2021, 36, 109421.
16. Shen, Y.; Li, F.; Szewczyk, M. M.; Halabelian, L.; Park, K. S.; Chau, I.; Dong, A.; Zeng, H.; Chen, H.; Meng, F.; Barsyte-Lovejoy, D.; Arrowsmith, C. H.; Brown, P.; Liu, J.; Vedadi, M.; Jin, J. Discovery of a First-in-class Protein Arginine Methyltransferase 6 (PRMT6) Covalent Inhibitor. J. Med. Chem. 2020, 63, 5477-5487.
17. Shen, Y.; Gao, G.; Yu, X.; Kim, H.; Wang, L.; Xie, L.; Schwarz, M.; Chen, X.; Guccione, E.; Liu, J.; Bedford, M. T.; Jin, J. Discovery of First-in-Class Protein Arginine Methyltransferase 5 (PRMT5) Degraders. J. Med. Chem. 2020, 63, 9977-9989.
18. Shen, Y.; McCorvy, J. D.; Martini, M. L.; Rodriguiz, R. M.; Progorelov, V. M.; Ward, K. M.; Wetsel, W. C.; Liu, J.; Roth, B. L.; Jin, J. D2 Dopamine Receptor G protein-biased Partial Agonists Based on Cariprazine. J. Med. Chem. 2019, 62, 4755-4771.
19. Fong, J. Y.; Pignata, L.; Goy, P. A.; Kawabata, K. C.; Lee, S. C.; Koh, C. M.; Musiani, D.; Massignani, E.; Kotini, A. G.; Penson, A.; Wun, C. M.; Shen, Y.; Schwarz, M.; Low, D. H.; Rialdi, A.; Ki, M.; Wollmann, H.; Mzoughi, S.; Gay, F.; Thompson, C.; Hart, T.; Barbash, O.; Luciani, G. M.; Szewczyk, M. M.; Wouters, B. J.; Delwel, R.; Papapetrou, E. P.; Barsyte-Lovejoy, D.; Arrowsmith, C. H.; Minden, M. D.; Jin, J.; Melnick, A.; Bonaldi, T.; Abdel-Wahab, O.; Guccione, E. Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation. Cancer Cell 2019, 36, 194-209, e9.
20. Zhu, Y.; He, X.; Lin, Y. C.; Dong, H.; Zhang, L.; Chen, X.; Wang, Z.; Shen, Y.; Li, M.; Wang, H.; Sun, J.; Nguyen, L. X.; Zhang, H.; Jiang, W.; Yang, Y.; Chen, J.; Muschen, M.; Chen, C. W.; Konopleva, M. Y.; Sun, W.; Jin, J.; Carlesso, N.; Marcucci, G.; Luo, Y.; Li, L. Targeting PRMT1-Mediated FLT3 Methylation Disrupts Maintenance of MLL-rearranged Acute Lymphoblastic Leukemia. Blood 2019, 134, 1257-1268.
21. He, X.; Zhu, Y.; Lin, Y. C.; Li, M.; Du, J.; Dong, H.; Sun, J.; Zhu, L.; Wang, H.; Ding, Z.; Zhang, L.; Zhang, L.; Zhao, D.; Wang, Z.; Wu, H.; Zhang, H.; Jiang, W.; Xu, Y.; Jin, J.; Shen, Y.; Perry, J.; Zhao, X.; Zhang, B.; Liu, S.; Xue, S. L.; Shen, B.; Chen, C. W.; Chen, J.; Khaled, S.; Kuo, Y. H.; Marcucci, G.; Luo, Y.; Li, L. PRMT1-mediated FLT3 arginine methylation promotes maintenance of FLT3-ITD(+) Acute Myeloid Leukemia. Blood 2019, 134, 548-560.
22. Scheer, S.; Ackloo, S.; Medina, T. S.; Schapira, M.; Li, F.; Ward, J. A.; Lewis, A. M.; Northrop, J. P.; Richardson, P. L.; Kaniskan, H. Ü.; Shen, Y.; Liu, J.; Smil, D.; McLeod, D.; Zepeda-Velazquez, C. A.; Luo, M.; Jin, J.; Barsyte-Lovejoy, D.; Huber, K. V. M.; De Carvalho, D. D.; Vedadi, M.; Zaph, C.; Brown, P. J.; Arrowsmith, C. H. A chemical biology toolbox to study protein methyltransferases and epigenetic signaling. Nat. Commun. 2019, 10, 19.
23. Zhang, T.; Wu, J.; Ungvijanpunya, N.; Jackson-Weaver, O.; Gou, Y.; Feng, J.; Ho, T. V.; Shen, Y.; Liu, J.; Richard, S.; Jin, J.; Hajishengallis, G.; Chai, Y.; Xu, J. Smad6 Methylation Represses NFκB Activation and Periodontal Inflammation. J. Dent. Res. 2018, 7, 810-819.
24. Shen, Y.; Szewczyk, M. M.; Eram, M. S.; Smil, D.; Kaniskan, H. Ü.; de Freitas, R. F.; Senisterra, G.; Li, F.; Schapira, M.; Brown, P. J.; Arrowsmith, C. H.; Barsyte-Lovejoy, D.; Liu, J.; Vedadi, M.; Jin, J. Discovery of a Potent, Selective and Cell-active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. J. Med. Chem. 2016, 59, 9124-9139.
25. Eram, M. S.;# Shen, Y.;# Szewczyk, M.; Wu, H.; Senisterra, G.; Li, F.; Butler, K. V.; Kaniskan, H. Ü.; Speed, B. A.; dela Seña, C.; Dong, A.; Zeng, H.; Schapira, M.; Brown, P. J.; Arrowsmith, C. H.; Barsyte-Lovejoy, D.; Liu, J.; Vedadi, M.; Jin, J. A Potent, Selective and Cell-active Inhibitor of Human Type I Protein Arginine Methyltransferases. ACS Chem. Biol. 2016, 11, 772-781. (#共同一作)
26. Kaniskan, H. U.; Eram, M. S.; Liu, J.; Smil, D.; Martini, M. L.; Shen, Y.; Santhakumar, V.; Brown, P. J.; Arrowsmith, C. H.; Vedadi, M.; Jin, J. Design and synthesis of selective, small molecule inhibitors of coactivator-associated arginine methyltransferase 1 (CARM1). MedChemComm 2016, 7, 1793-1796.
27. Chen, X.; McCorvy, J. D.; Fischer, M. G.; Butler, K. V.; Shen, Y.; Roth, B. L.; Jin, J. Discovery of G Protein-biased D2 Dopamine Receptor Partial Agonists. J. Med. Chem. 2016, 59, 10601-10618.
发表专利:
1. Jian Jin; Jing Liu; Yudao Shen; Ernesto Guccione; Martin Walsh; Almudena Bosch; Megan Sch warz ; Protein arginine methyltransferase 5 (PRMT5) degradation/disruption compounds and methods of use for treating PRMT5-mediated diseases, 2019-8-29, WIPO, WO2019165189A1.
2. Jian Jin; Marta Filizola; Aneel Aggarwal; Samir Parekh; Abhijeet Kapoor; Shashidhar Jitian; H Kaniskan; Jianping Hu; Yudao Shen; Fanye Meng; Lihuai Qin; Yulin Han; Xufen Yu; Chengwei Zha ng; Prashasti Kumar; Rinku Jain; Clement Lee ; SOX11 inhibitors for treating mantle cell lymphoma, 2021-12-23 WIPO, WO2021257544A1.
先后发现了多个高活性、高选择性并有细胞活性的PRMTs抑制剂和降解剂,包括Type I PRMTs 抑制剂MS023; PRMT4 和PRMT6双重抑制剂 MS049;PRMT6共价抑制剂MS117;PRMT6变构抑制剂SGC6870;PRMT5降解剂MS4322。以上的一系列化学探针被发表在国际知名的药物化学期刊上,且被广泛用于动物模型研究中,并取得积极的实验结果,部分实验数据被包含发表在高影响因子的学术期刊上 (Cell (2021), Cell Reports (2021), Nature Communications (2019), Bloods (2019), Cancer Cells (2019), Bloods (2019))。其中的四个抑制剂MS023、MS049、MS117和SGC6870已被众多试剂公司作为产品销售。此外,发现了选择性激活G蛋白信号通路的多巴胺受体 (D2R) 偏向配体 MS1768。
代表作:
1. Shen, Y.;# Li, F.;# Szewczyk, M. M.;# Halabelian, L.;# Chau, I.; Eram, M. S.; Dela Sena, C.; Park, K. S.; Meng, F.; Chen, H.; Zeng, H.; McLeod, D.; Zepeda-Velazquez, C. A.; Campbell, R. M.; Mader, M. M.; Watson, B. M.; Schapira, M.; Arrowsmith, C. H.; Al-Awar, R.; Barsyte-Lovejoy, D.; Kaniskan, H. U.; Brown, P. J.;* Vedadi, M.;* Jin, J.* A First-in-class, Highly Selective and Cell-active Allosteric Inhibitor of Protein Arginine Methyltransferase 6 (PRMT6). J. Med. Chem. 2021, 64, 3697-3796. (featured article)
2. Shen, Y.; # Gao, G.; # Yu, X.; Kim, H.; Wang, L.; Xie, L.; Schwarz, M.; Chen, X.; Guccione, E.; Liu, J.; Bedford, M. T.;* Jin, J.* Discovery of First-in-Class Protein Arginine Methyltransferase 5 (PRMT5) Degraders. J. Med. Chem. 2020, 63, 9977-9989.
3. Shen, Y.;# Li, F.;# Szewczyk, M. M.;# Halabelian, L.; Park, K. S.; Chau, I.; Dong, A.; Zeng, H.; Chen, H.; Meng, F.; Barsyte-Lovejoy, D.; Arrowsmith, C. H.; Brown, P.; Liu, J.;* Vedadi, M.;* Jin, J.* Discovery of a First-in-class Protein Arginine Methyltransferase 6 (PRMT6) Covalent Inhibitor. J. Med. Chem. 2020, 63, 5477-5487.
4. Shen, Y.;# McCorvy, J. D.;# Martini, M. L.; Rodriguiz, R. M.; Progorelov, V. M.; Ward, K. M.; Wetsel, W. C.; Liu, J.;* Roth, B. L.;* Jin, J.* D2 Dopamine Receptor G protein-biased Partial Agonists Based on Cariprazine. J. Med. Chem. 2019, 62, 4755-4771.
5. Eram, M. S.;# Shen, Y.;# Szewczyk, M.;# Wu, H.; Senisterra, G.; Li, F.; Butler, K. V.; Kaniskan, H. Ü.; Speed, B. A.; dela Seña, C.; Dong, A.; Zeng, H.; Schapira, M.; Brown, P. J.; Arrowsmith, C. H.; Barsyte-Lovejoy, D.; Liu, J.;* Vedadi, M.;* Jin, J.* A Potent, Selective and Cell-active Inhibitor of Human Type I Protein Arginine Methyltransferases. ACS Chem. Biol. 2016, 11, 772-781. (共同一作)
6. Shen, Y.;# Szewczyk, M. M.;# Eram, M. S.;# Smil, D.; Kaniskan, H. Ü.; de Freitas, R. F.; Senisterra, G.; Li, F.; Schapira, M.; Brown, P. J.; Arrowsmith, C. H.; Barsyte-Lovejoy, D.; Liu, J.;* Vedadi, M.;* Jin, J.* Discovery of a Potent, Selective and Cell-active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. J. Med. Chem. 2016, 59, 9124-9139.

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