许永课题组

导师简介

教育经历：

2004年毕业于中科院上海药物所，获药学博士学位；

2004至2006年在中科院上海有机所进行博士后研究；

2006年至2011年在美国Van Andel研究所进行博士后研究

主要研究方向（导师）

抗肿瘤小分子药物的设计、合成与生物活性的测试

导师主持、参与的科研项目（含科研获奖等情况）

科技部国家重点研发计划（2020年，2016年，2013年）；基金委面上项目；

中科院“百人计划”择优支持项目；

中国科学院科技服务网络计划（STS计划）区域重点项目；

中科院“个性化药物”战略性先导科技专项（A类）

2020年 国务院特殊津贴

2018年 广东省自然科学奖二等奖 （第一完成人）

2016年 美国前列腺癌基金会挑战奖

代表性论文（导师）

1. Li Q, Yao B, Zhao S, Lu Z, Zhang Y, Xiang Q, Wu X, Yu H, Zhang C, Li J, Zhuang X, Wu D, Li Y, Xu Y. Discovery of a Highly Selective and H435R-Sensitive Thyroid Hormone Receptor β Agonist.

J Med Chem. 2022, 65, 7193-7211.

2. Li J, Zhang C, Xu H, Wang C, Dong R, Shen H, Zhuang X, Chen X, Li Q, Lu J, Zhang M, Wu X, Loomes KM, Zhou Y, Zhang Y, Liu J, Xu Y. Structure- Based Discovery and Optimization of Furo[3,2-c]pyridin-4(5H)-one Derivatives as Potent and Second Bromodomain (BD2)-Selective Bromo and Extra Terminal Domain (BET) Inhibitors.

J Med Chem. 2022, 65, 5760-5799..

3. Zhang MF, Luo XY, Zhang C, Wang C, Wu XS, Xiang QP, Xu Y, Zhang Y. Design, synthesis and pharmacological characterization of N-(3-ethylbenzo[d] isoxazol-5-yl) sulfonamide derivatives as BRD4 inhibitors against acute myeloid leukemia.

Acta Pharmacol Sin. 2022 Mar 9:1-14. doi: 10.1038/s41401-022-00881-y

4. Li W, Zhang C, Zhang HE, Dong R, Liu JY, Wang CM, Wang M, Wang YW, Wang C, Zhang Y, Shi L, Xu Y, Sun LP. Design, synthesis, and anticancer evaluation of ammosamide B with pyrroloquinoline derivatives as novel BRD4 inhibitors.

Bioorg Chem. 2022, 127, 105917.

5. Xiang Q, Luo G, Zhang C, Hu Q, Wang C, Wu T, Xu H, Hu J, Zhuang X, Zhang M, Wu S, Xu J, Zhang Y, Liu J, Xu Y. Discovery, optimization and evaluation of 1-(indolin-1-yl)ethan-1-ones as novel selective TRIM24/BRPF1 bromodomain inhibitors.

Eur J Med Chem. 2022, 236, 114311.

6. Xiang Q, Wang C, Wu T, Zhang C, Hu Q, Luo G, Hu J, Zhuang X, Zou L, Shen H, Wu X, Zhang Y, Kong X, Liu J, Xu Y. Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.

J Med Chem. 2022, 65, 785-810

7. Wu X#, Shen H#, Zhang Y#, Wang C, Li Q, Zhang C, Zhuang X, Li C, Shi Y, Xing Y, Xiang Q, Wu D, Liu J, Xu Y*. Discovery and characterization of benzimidazole derivative XY123 as a selective, and orally available RORγ inverse agonist.

J Med Chem. 2021, 64, 8775-8797

8. Dong R, Zhang C, Wang C, Zhou X, Li W, Zhang JY, Wang M, Xu Y, Sun LP. Design, synthesis and anticancer evaluation of 3-methyl-1H-indazole derivatives as novel selective bromodomain-containing protein 4 inhibitors.

Bioorg Med Chem. 2021, 55, 116592

9. Wu T#, Xiang Q#, Wang C#, Wu C, Zhang C, Zhang M, Liu Z, Zhang Y*, Xiao L*, Xu Y*. Y06014 is a selective BET inhibitor for the treatment of prostate cancer.（共同通讯）

Acta Pharmacol Sin. 2021 Mar 2. doi: 10.1038/s41401-021-00614-7.

10. Hu Q, Wang C, Xiang Q, Zhang C, Zhang M, Xue X, Luo G, Liu X, Wu X, Zhang Y, Wu D, Xu, Y*. Discovery and optimization of novel N-benzyl-3,6-dimethylbenzo[d]isoxazol-5-amine derivatives as potent and selective TRIM24 bromodomain inhibitors with potential anti-cancer activities.

Bioorganic Chemistry, 2020, 94, 103424.

11. Wu X, Zhang Y, Xu Y*. Discovery of the First Low Nanomolar Liver Receptor Homolog-1 (LRH-1) Agonist.

J Med Chem. 2019, Nov 21. doi: 10.1021/acs.jmedchem.9b01753.

12. Zou L#, Xiang Q#, Xue X#, Zhang C, Li C, Wang C, Li Q, Wang R, Wu S, Zhou Y, Zhang Y, Xu Y*. Y08197 is a novel and selective CBP/EP300 bromodomain inhibitor for the treatment of prostate cancer.

Acta Pharmacol Sin. 2019, 40, 1436-1447.

13. Zhang Y#, Wu X#, Xue X#, Li C, Wang J, Wang R, Zhang C, Wang C, Shi Y, Zou L, Li Q, Huang Z, Hao X, Loomes K, Wu D, Chen HW, Xu J, Xu Y*. Discovery and Characterization of XY101, a Potent, Selective, and Orally Bioavailable RORγ Inverse Agonist for Treatment of Castration-Resistant Prostate Cancer.

J Med Chem. 2019, 62, 4716-4730

14. Xue X, Zhang Y, Wang C, Zhang M, Xiang Q, Wang J, Wang A, Li C, Zhang C, Zou L, Wang R, Wu S, Lu Y, Chen H, Ding K, Li G, Xu Y*. Benzoxazinone-containing 3,5-dimethylisoxazole derivatives as BET bromodomain inhibitors for treatment of castration-resistant prostate cancer.

Eur J Med Chem. 2018, 152, 542-559

15. Xiang Q#, Zhang Y#, Li J#, Xue X, Wang C, Song M, Zhang Z, Wang R, Li C, Wu C, Zhou Y, Yang X, Li G, Ding K, Xu Y*. Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer.

ACS Med Chem Lett. 2018, 9, 262-267

16. Zhang M#, Zhang Y#, Song M#, Xue X, Wang J, Wang C, Zhang C, Li C, Xiang Q, Wu X, Wu C, Dong B, Xue We, Zhou Y, Chen H, Wu D, Ding K, Xu Y*. Structure-Based Discovery and Optimization of Benzo[d]isoxazole Derivatives as Potent and Selective BET Inhibitors as Potential Treatment for Castration-Resistant Prostate Cancer (CRPC).

J Med Chem, 2018. 61, 3037-3058

17. Xiang Q#, Wang C#, Zhang Y, Xue X, Song M, Zhang C, Li C, Wu C, Li K, Hui X, Zhou Y, Smaill JB, Patterson AV, Wu D, Ding K, Xu Y.* Discovery and optimization of 1-(1H-indol-1-yl)ethanone derivatives as CBP/EP300 bromodomain inhibitors for the treatment of castration-resistant prostate cancer.

Eur J Med Chem. 2018, 147, 238-252

18. Wu X#, Wang R#, Xing Y#, Xue X, Zhang Y, Lu Y, Song Y, Luo X, Wu C, Zhou Y, Jiang J, Xu Y*. Discovery and structural optimization of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-ones as RORc inverse agonists.

Acta Pharmacol Sin, 2016, 37: 1516-1524.

19. Zhou Y#, Nie T#, Zhang Y, Song M, Li K, Ding M, Ding K, Wu D*, Xu Y*.The discovery of novel and selective fatty acid binding protein 4 inhibitors by virtual screening and biological evaluation. （共同通讯）

Bioorg Med Chem, 2016, 24: 4310-4317.

20. Wang, J.; Zou, J.X.; Xue, X.; Cai, D.; Zhang, Y.; Duan, Z.; Xiang, Q.; Yang, J.C.; Louie, M.C.; Borowsky, A.D.; Gao, A.C,; Evans, C.P.; Lam, K.S.; Xu, J.; Kung, H.J.; Evans, R.M.; Xu, Y.*; Chen, H.W.*; ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer. （共同通讯）

Nat Med, 2016, 22: 488-496. (Highlighted by Nature, Nature Review Urology)

21. Song, Y.; Xue, X.; Wu, X.; Wang, R.; Xing, Y.; Yan, W.; Zhou, Y.; Qian, C-N.; Zhang, Y.*; Xu, Y.*; Identification of N-phenyl-2-(N-phenylphenyl sulfonamido) acetamides as new RORγ inverse agonists: Virtual screening, structure-based optimization, and biological evaluation. （共同通讯）

Eur J Med Chem, 2016, 116, 13-26.

22. Xue, X.; Zhang, Y.; Liu, Z.; Song, M.; Xing, Y.; Xiang, Q.; Wang, Z.; Tu, Z.; Zhou, Y.; Ding, K.; Xu Y*. Discovery of benzo[cd]indol-2(1H)-ones as potent and specific BET bromodomain inhibitors: structure-based virtual screening, optimization, and biological evaluation.

J Med Chem, 2016, 59, 1565-1579.

23. Zhao, X.; Zhang, Z. W.; Cui, W.; Chen, S. W.; Zhou, Y.; Dong, J. H.; Jie, Y. L.; Wan, J. T.; Xu Y*; Hu, W. H*. Identification of camphor derivatives as novel M2 ion channel inhibitors of influenza A virus. （共同通讯）

Medchemcomm, 2015, 6, 727-731.

24. Zhang, Y.; Luo, X. Y.; Wu, D. H.*; Xu Y*. ROR nuclear receptors: structures, related diseases, and drug discovery. （共同通讯）

Acta Pharmacol Sin, 2015, 36, 71-87.

25. Zhang, Y.; Xue, X.; Jin, X.; Song, Y.; Li, J.; Luo, X.; Song, M.; Yan, W.; Song, H.; Xu, Y*. Discovery of 2-oxo-1,2-dihydrobenzo [cd]indole-6-sulfonamide derivatives as new RORgamma inhibitors using virtual screening, synthesis and biological evaluation.

Eur J Med Chem, 2014, 78, 431-441.

26. Cao, M.; Liu, X.; Zhang, Y.; Xue, X.; Zhou, X. E.; Melcher, K.; Gao, P.; Wang, F.; Zeng, L.; Zhao, Y.; Zhao, Y.; Deng, P.; Zhong, D.; Zhu, J. K.*; Xu, H. E.*; Xu, Y*. An ABA-mimicking ligand that reduces water loss and promotes drought resistance in plants. （共同通讯）

Cell Res, 2013, 23, 1043-1054. (Highlighted by Nature Review Genetics, Cell)