|
2011.09 – now |
Guangzhou Institutes of Biomedicine and Health, CAS /Principle Investigator |
|
2006.06 – 2011.08 |
Van Andel Research Institute, Michigan, USA/Postdoctoral fellow |
|
2004.08 – 2006.05 |
Shanghai Institute of Organic Chemistry, CAS/Postdoctoral fellow |
|
2001.09 – 2004.07 |
Shanghai Institute of Materia Medica, CAS/Ph.D |
|
1998.09 – 2001.07 |
Liaoning Normal College, M.Sc., Phycial Chemistry |
Dr. Yong Xu mainly focuses on the clinical-need-oriented basic research on personalized medicine with the aim of identifying and validating drug targets and lead compounds. By combining AI-aided drug design, medicinal chemistry, and structural biology, significant achievements have been achieved in the field of lead compounds discovery and target validation for hormone receptors and epigenetic receptors. His research is focused on the signaling mechanisms of important hormones and related epigenetics proteins, trying to solve fundamental questions that have a broad impact on human health and disease such as prostate cancer, leukemia, lung cancer.
2016 Prostate Cancer Foundation (PCF) Challenge Award, USA
2019 Guangdong Science and Technology Award, Second Prize, China
He identified and validated RORγ as novel therapeutic target for lethal castration resistant prostate cancer. For lead development, a series of potent compounds with drug like properties was identified for RORγ (AR driver), BRD4 (AR coregulator). Dr. Xu has published over 100 SCI indexed papers in Nat Med, Cell Res, Nat Struct & Mol Biol, J Med Chem. Some research works were highlighted in Nature, Nat Rev Urol and other journals. Dr. Xu was awarded the "2016 Movember-PCF Challenge Award" by Prostate Cancer Foundation, the “2018 Guangdong Natural Science Award”.
Patents:
1. Xu Y et al, A type of indole compounds and its application. Patents for Inventions, ZL202110124967.0, Authorization date (09 June 2023), China.
2. Xu Y et al, A type of indole compounds and its application. Patents for Inventions, ZL201710480445.8, Authorization date (02 June 2023), China.
3. Xu Y et al, A type of benzo six-membered nitrogen heterocyclic compounds and its preparation method and application. Patents for Inventions, ZL201810089988.1, Authorization date (21 October 2022), China.
4. Xu Y et al, A type of indolizine compounds and its preparation method and application. Patents for Inventions, ZL201811531971.3, Authorization date (04 October 2022), China.
5. Xu Y et al, Tetrahydroquinoline related bicyclic compounds and their applications. Patents for Inventions, ZL201610064772.0, Authorization date (23 September 2022), China.
6. Xu Y et al, A type of 2-oxo-1,2-dihydrobenzo [cd] indole compounds. Patents for Inventions, ZL202010548432.1, Authorization date (18 March 2022), China.
7. Xu Y et al, A benzo[d]isoxazole compounds and its preparation method and application. Patents for Inventions, ZL201710481251.X, Authorization date (04 March 2022), China.
8. Xu Y et al, A type of biphenylamine compounds and its application. Patents for Inventions, ZL201910202909.8, Authorization date (29 June 2021), China.
9. Xu Y et al, A type of 2-oxo-1,2-dihydrobenzo [cd] indole compounds and its pharmaceutical composition and use. Patents for Inventions, ZL201510043387.3, Authorization date (08 December 2020), China.
10. Xu Y et al, N-phenylamide compounds and their applications. Patents for Inventions, ZL201510117768.1, Authorization date (09 April 2019), China.
11. Xu Y et al, 2-oxo-1,2-dihydrobenzo [cd] indole compound and use thereof. Patents for Inventions, US10183010B2, Authorization date (22 January 2019), United States.
12. Xu Y et al, A type of benzo[d]isoxazole compound and their applications. Patents for Inventions, ZL201510518582.7, Authorization date (05 June 2019), China.
13. Xu Y et al, 2-Oxo-1,2-dihydrobenzo [cd] indole-6-sulfonamide compounds and their compositions and applications. Patents for Inventions, ZL201410821535.5, Authorization date (20 March 2018), China.
1. Chen Z, Yang H, Zhang Y, Lyu X, Shi Q, Zhang C, Wang X, Wang Z, Zhang Y, Deng Y, Wang Y, Huang Y, Xu Y*, Huang X*, Li Y*. Discovery of CZL-046 with an (S)-3-fluoropyrrolidin-2-one scaffold as a p300 bromodomain inhibitor for the treatment of multiple myeloma. J Med Chem. 2024, doi: 10.1021/acs.jmedchem.4c01984.
2. Hu J, Xu H, Wu T, Zhang C, Shen H, Dong R, Hu Q, Xiang Q, Chai S, Luo G, Chen X, Huang Y, Zhao X, Peng C, Wu X, Lin B, Zhang Y*, Xu Y*. Discovery of highly potent and efficient CBP/p300 degraders with strong in vivo antitumor activity. J Med Chem. 2024, 67, 6952-6986.
3. Wu T, Hu J, Zhao X, Zhang C, Dong R, Hu Q, Xu H, Shen H, Zhang X, Zhang Y, Lin B, Wu X*, Xiang Q*, Xu Y*. Discovery of a promising CBP/p300 degrader XYD129 for the treatment of acute myeloid leukemia. J Med Chem. 2024, 67, 9194-9213.
5. Wu T, Lu Z, Yu H, Wu X, Liu Y*, Xu Y*. Liver receptor homolog-1: structures, related diseases, and drug discovery. Acta Pharmacol Sin. 2024, 45, 1571-1581.
6. Wu X*, Luo X, Li C, Zhao X, Zhang C, Chen X, Lu Z, Wu T, Yu H, Peng C, Hu Q, Shen H, Xu Y*, Zhang Y*. Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer. Acta Pharmacol Sin. 2024, 45(9):1964-1977.
7. Yu S, Zhang Y, Yang J, Xu H, Lan S, Zhao B, Luo M, Ma X, Zhang H, Wang S, Shen H, Zhang Y, Xu Y*, Li R*. Discovery of (R)-4-(8-methoxy-2-methyl-1-(1-phenylethy)-1H-imidazo [4,5-c] quinnolin-7-yl)-3,5-dimethylisoxazole as a potent and selective BET inhibitor for treatment of acute myeloid leukemia (AML) guided by FEP calculation. Eur J Med Chem. 2024, 263, 115924.
8. Zhu R, Li J*, Dong R, Hu Q, Chen Z, Chen X, Zhong Z, Xiang Q, Huang C, Lin B, Wu X, Zhang Y, Zhao L*, Xu Y*. Optimization of the synthesis of BET BD2 selective inhibitor XY153. Chem Biodivers. 2024, 21, e202301584.
9. Jiang W, Hou Q, Xu H, Yang K, Wang X, Zhang K, Zeng Y, Li W, Wang B, Luo G, Zhao X, Shen H, Xu Y*, Wu X*. Discovery of Novel Phenoxyaryl Pyridones as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with High Selectivity for the Second Bromodomain (BD2) to Potentially Treat Acute Myeloid Leukemia. J Med Chem. 2024, 67, 1513-1532.
10. Xiang Q*, Wu T, Zhang C, Wang C, Xu H, Hu Q, Hu J, Luo G, Zhuang X, Wu X, Zhang Y*,Xu Y*. Discovery of a potent and selective CBP bromodomain inhibitor (Y08262) for treating acute myeloid leukemia. Bioorg Chem. 2024, 142, 106950.
11. Li J, Zhu R, Zhuang X, Zhang C, Shen H, Wu X, Zhang M, Huang C, Xiang Q, Zhao L,Xu Y*, Zhang Y*. Rational design, synthesis and biological evaluation of benzo[d]isoxazole derivatives as potent BET bivalent inhibitors for potential treatment of prostate cancer. Bioorg Chem. 2023, 135, 106495.
12. Zhao S, Ali AS, Kong X, Zhang Y, Liu X, Skidmore MA, Forsyth CM, Savage GP, Wu D*, Xu Y*, Francis CL*. 1-Benzyloxy-5-phenyltetrazole derivatives highly active against androgen receptor-dependent prostate cancer cells. Eur J Med Chem. 2023, 246, 114982.
13. 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.
14. 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.
15. 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.
16. 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.
17. Xu H, Luo G, Wu T, Hu J, Wang C, Wu X, Zhang Y*, Xu Y*, Xiang Q*. Structural insights revealed by the cocrystal structure of CCS1477 in complex with CBP bromodomain. Biochem Biophys Res Commun. 2022, 623, 17-22.
18. Li W, Zhang C, Zhang HE, Dong R, Liu J, 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.
19. Zhang M*, Luo X, Zhang C, Wang C, Wu X, Xiang Q, 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, 43, 2735-2748.
20. Wu X, Shen H, Zhang Y, Wang C, Li Q, Zhang C, Zhuang X, Li C, Shi Y, Xing Y, Xiang Q, Xu J, Wu D, Liu J, Xu Y*. Discovery and characterization of benzimidazole derivative XY123 as a potent, selective, and orally available RORγ inverse agonist. J Med Chem. 2021, 64, 8775-8797.
21. Dong R, Zhang C, Wang C, Zhou X, Li W, Zhang J, 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.
22. 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. Acta Pharmacol Sin. 2021, 42, 2120-2131.
23. 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.
24. Wu X, Zhang Y, Xu Y*. Discovery of the first low nanomolar liver receptor homolog-1 (LRH-1) agonist. J Med Chem. 2019, 62, 11019-11021.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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. Bioorg Med Chem, 2016, 24: 4310-4317.
33. Wang, J, Zou JX, Xue X, Cai D, Zhang Y, Duan Z, Xiang Q, Yang JC, Louie MC, Borowsky AD, Gao AC, Evans CP, Lam KS, Xu J, Kung HJ, Evans RM, Xu Y*, Chen H*. ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer. Nat Med. 2016, 22: 488-496. (Highlighted by Nature, Nature Review Urology)
34. Song Y, Xue X, Wu X, Wang R, Xing Y, Yan W, Zhou Y, Qian CN, 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. Eur J Med Chem. 2016, 116, 13-26.
35. 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.
36. Zhao X, Zhang Z, Cui W, Chen S, Zhou Y, Dong J, Jie Y, Wan J, Xu Y*, Hu W*. Identification of camphor derivatives as novel M2 ion channel inhibitors of influenza A virus. Med Chem Comm. 2015, 6, 727-731.
37. Zhang Y, Luo X, Wu D*, Xu Y*. ROR nuclear receptors: structures, related diseases, and drug discovery. Acta Pharmacol Sin. 2015, 36, 71-87.
38. 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-sulfonamidederivatives as new RORγ inhibitors using virtual screening, synthesis and biological evaluation. Eur J Med Chem. 2014, 78, 431-441.
39. Cao M, Liu X, Zhang Y, Xue X, Zhou X, Melcher K, Gao P, Wang F, Zeng L, Zhao Y, Zhao Y, Deng P, Zhong D, Zhu J*, Xu H*, Xu Y*. An ABA-mimicking ligand that reduces water loss and promotes drought resistance in plants. Cell Res. 2013, 23, 1043-1054. (Highlighted by Nature Review Genetics, Cell)
42. Xu Y, Zhang T, Chen M. Combining 3D-QSAR, docking, molecular dynamics and MM/PBSA methods to predict binding modes for nonsteroidal selective modulator to glucocorticoid receptor. Bioorg Med Chem Lett. 2009, 19, 393-396.
43. Xu Y, Wang R. A computational analysis of the binding affinities of FKBP12 inhibitors using the MM-PB/SA method. Proteins. 2006, 64, 1058-1068.
44. Xu Y, Liu H, Niu C, Luo C, Luo X, Shen J, Chen K, Jiang H. Molecular docking and 3D QSAR studies on 1-amino-2-phenyl-4-(piperidin-1-yl)-butanes based on the structural modeling of human CCR5 receptor. Bioorg Med Chem, 2004, 12, 6193-6208.