邓贤明/Xianming Deng

邓贤明教授博导

邓贤明,博士,厦门大学生命科学学院教授,分子影像暨转化医学研究中心兼聘教授。2001年,毕业于厦门大学化学系化学专业,获理学学士学位;2006年,毕业于中科院上海有机化学研究所有机化学专业,获理学博士学位,导师唐勇研究员;2006年至2011年,在哈佛医学院Dana-Farber癌症研究所从事博士后研究,导师Nathanael S. Gray 教授;2011年10月起,为厦门大学生命科学学院“闽江学者”特聘教授,博士生导师,入选中组部第二批“青年千人”计划。

研究方向:化学生物学和药物化学。在化学生物学方面,我们集中于设计并合成新颖的针对蛋白激酶(Protein Kinase)和表观遗传蛋白(Epigenetic Enzyme)的小分子抑制剂,并运用这些功能小分子为工具,发现和解决信号传导通路、神经生物学和癌症中的新问题。在药物化学方面,以化学生物学研究成果为基础,结合传统的药物化学手段(构效关系研究、药代动力学和毒理学研究)进一步优化小分子工具化合物,以期发展针对癌症等相关疾病的“靶向治疗”药物。

研究成果:研究结果发表于Nature, Cancer Cell, Nat. Chem. Biol., J. Am. Chem. Soc., J. Med. Chem. 等杂志。现已发表论文35篇,其中通讯作者、第一作者(含共同第一作者)16篇,同时申请国际专利3项。同时获邀在国际重要学术会议“7th Protein Kinases in Drug Discovery”作邀请报告。

Email: xmdeng@xmu.edu.cn

Phone: 0592-2184180

Fax: 0592-2181722

Our research is focused on two major areas: chemical biology and medicinal chemistry. At the interface of chemistry and biology, we use organic synthesis to create new chemical tools for studying biological problems in human health and disease. These functional small-molecule tools are applied to control and elucidate cellular signal transduction in  cancer, stem cell, and neural diseases. Second, we pursue established medicinal chemistry approaches including structure activity relationship (SAR) study and pharmacokinetics modification to optimize pre-clinical drug candidates. We're working to address the following general questions: a) How can we develop small-molecule modulators with selectivity towards desired targets such as protein kinases and epigenetic enzymes? b) How can we use discovered-small-molecule tools to dissect the  molecular signaling pathways? c) How can we develop the 'lead' of targeted-drug from the tool compound?  

发表的代表性论文和专利/Publications (*Corresponding author, ¶ Co-first authorship)

1. Deng, X. *; Choi, H. G.; Buhrlage, S. J.; Gray, N. S. * Leucine-rich repeat kinase 2 (LRRK2) inhibitors: a patent review (2006-2011). Expert  opinion on therapeutic patents 2012, 22, 1415-26.

2. Garnett, M. J.; Edelman, E. J.; Heidorn, S. J.; Greenman, C. D.; Dastur, A.; Lau, K. W.; Greninger, P.; Thompson, I. R.; Luo, X.; Soares, J.; Liu, Q.; Iorio, F.; Surdez, D.; Chen, L.; Milano, R. J.; Bignell, G. R.; Tam, A. T.; Davies, H.; Stevenson, J. A.; Barthorpe, S.; Lutz, S. R.; Kogera, F.; Lawrence, K.; McLaren-Douglas, A.; Mitropoulos, X.; Mironenko, T.; Thi, H.; Richardson, L.; Zhou, W.; Jewitt, F.; Zhang, T.; O'Brien, P.; Boisvert, J. L.; Price, S.; Hur, W.; Yang, W.; Deng, X.; Butler, A.; Choi, H. G.; Chang, J. W.; Baselga, J.; Stamenkovic, I.; Engelman, J. A.; Sharma, S. V.; Delattre, O.; Saez-Rodriguez, J.; Gray, N. S.; Settleman, J.; Futreal, P. A.; Haber, D. A.; Stratton, M. R.; Ramaswamy, S.; McDermott, U.; Benes, C. H. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature 2012, 483, 570-5.

3. Deng, X.; Zhou, W.; Weisberg, E.; Wang, J.; Zhang, J.; Sasaki, T.; Nelson, E.; Griffin, J. D.; Janne, P. A.; Gray, N. S. An amino-indazole scaffold with spectrum selective kinase inhibition of FLT3, PDGFRalpha and kit. Bioorg. Med. Chem. Lett. 2012, 22, 4579-84.

4. Deng, X. *; Gray, N. S. * (WO2011141756) pyrazolopyridines as inhibitors of the kinase LRRK2: a patent evaluation. Expert Opin. Ther. Pat. 2012, 22, 709-713.

5. Kwiatkowski, N. ¶; Deng, X. ¶; Wang, J.; Tan, L.; Villa, F.; Santaguida, S.; Huang, H. C.; Mitchison, T.; Musacchio, A.; Gray, N. Selective aurora kinase inhibitors identified using a taxol-induced checkpoint sensitivity screen. ACS Chem. Biol.  2012, 7, 185-96.
Rated 'recommended' 6.0 by Faculty of 1000.

6. Deng, X. ¶; Dzamko, N. ¶; Prescott, A.; Davies, P.; Liu, Q.; Yang, Q.; Lee, J. D.; Patricelli, M. P.; Nomanbhoy, T. K.; Alessi, D. R.; Gray, N. S. Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2. Nat. Chem. Biol.  2011, 7, 203-5.

7. Deng, X. ¶; Yang, Q. ¶; Kwiatkowski, N.; Sim, T.; McDermott, U.; Settleman, J. E.; Lee, J. D.; Gray, N. S. Discovery of a benzo[e]pyrimido-[5,4-b][1,4]diazepin-6(11H)-one as a Potent and Selective Inhibitor of Big MAP Kinase 1. ACS Med. Chem. Lett. 2011, 2, 195-200.

8. Deng, X. ¶; Wang, J. ¶; Zhang, J. ¶; Sim, T.; Kim, N. D.; Sasaki, T.; Luther, W., 2nd; George, R. E.; Janne, P. A.; Gray, N. S. Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors. ACS Med. Chem. Lett. 2011, 2, 379-384.

9. Miduturu, C. V. ¶; Deng, X. ¶; Kwiatkowski, N.; Yang, W.; Brault, L.; Filippakopoulos, P.; Chung, E.; Yang, Q.; Schwaller, J.; Knapp, S.; King, R. W.; Lee, J. D.; Herrgard, S.; Zarrinkar, P.; Gray, N. S. High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors. Chem. Biol.  2011, 18, 868-79.

10. Hammerman, P. S.; Sos, M. L.; Ramos, A. H.; Xu, C.; Dutt, A.; Zhou, W.; Brace, L. E.; Woods, B. A.; Lin, W.; Zhang, J.; Deng, X.; Lim, S. M.; Heynck, S.; Peifer, M.; Simard, J. R.; Lawrence, M. S.; Onofrio, R. C.; Salvesen, H. B.; Seidel, D.; Zander, T.; Heuckmann, J. M.; Soltermann, A.; Moch, H.; Koker, M.; Leenders, F.; Gabler, F.; Querings, S.; Ansen, S.; Brambilla, E.; Brambilla, C.; Lorimier, P.; Brustugun, O. T.; Helland, A.; Petersen, I.; Clement, J. H.; Groen, H.; Timens, W.; Sietsma, H.; Stoelben, E.; Wolf, J.; Beer, D. G.; Tsao, M. S.; Hanna, M.; Hatton, C.; Eck, M. J.; Janne, P. A.; Johnson, B. E.; Winckler, W.; Greulich, H.; Bass, A. J.; Cho, J.; Rauh, D.; Gray, N. S.; Wong, K. K.; Haura, E. B.; Thomas, R. K.; Meyerson, M. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discovery 2011, 1, 78-89.

11. Yang, Q. ¶; Deng, X. ¶; Lu, B. ¶; Cameron, M.; Fearns, C.; Patricelli, M. P.; Yates, J. R., 3rd; Gray, N. S.; Lee, J. D. Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell 2010, 18, 258-67.

12. Deng, X. ¶; Okram, B. ¶; Ding, Q. ¶; Zhang, J. ¶; Choi, Y.; Adrian, F. J.; Wojciechowski, A.; Zhang, G.; Che, J.; Bursulaya, B.; Cowan-Jacob, S. W.; Rummel, G.; Sim, T.; Gray, N. S. Expanding the diversity of allosteric bcr-abl inhibitors. J. Med. Chem. 2010, 53, 6934-46.

13. Deng, X.; Nagle, A.; Wu, T.; Sakata, T.; Henson, K.; Chen, Z.; Kuhen, K.; Plouffe, D.; Winzeler, E.; Adrian, F.; Tuntland, T.; Chang, J.; Simerson, S.; Howard, S.; Ek, J.; Isbell, J.; Tully, D. C.; Chatterjee, A. K.; Gray, N. S. Discovery of novel 1H-imidazol-2-yl-pyrimidine-4,6-diamines as potential antimalarials. Bioorg. Med. Chem. Lett. 2010, 20, 4027-31.

14. Zhang, J.; Adrian, F. J.; Jahnke, W.; Cowan-Jacob, S. W.; Li, A. G.; Iacob, R. E.; Sim, T.; Powers, J.; Dierks, C.; Sun, F.; Guo, G. R.; Ding, Q.; Okram, B.; Choi, Y.; Wojciechowski, A.; Deng, X.; Liu, G.; Fendrich, G.; Strauss, A.; Vajpai, N.; Grzesiek, S.; Tuntland, T.; Liu, Y.; Bursulaya, B.; Azam, M.; Manley, P. W.; Engen, J. R.; Daley, G. Q.; Warmuth, M.; Gray, N. S. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature 2010, 463, 501-6.

15. Weisberg, E.; Deng, X.; Choi, H. G.; Barrett, R.; Adamia, S.; Ray, A.; Moreno, D.; Kung, A. L.; Gray, N.; Griffin, J. D. Beneficial effects of combining a type II ATP competitive inhibitor with an allosteric competitive inhibitor of BCR-ABL for the treatment of imatinib-sensitive and imatinib-resistant CML. Leukemia 2010, 24, 1375-8.

16. Wang, Q.-G.; Deng, X.-M.; Zhu, B.-H.; Ye, L.-W.; Sun, X.-L.; Li, C.-Y.; Zhu, C.-Y.; Shen, Q.; Tang, Y. Tandem Michael addition/ylide epoxidation for the synthesis of highly functionalized cyclohexadiene epoxide derivatives. J. Am. Chem. Soc. 2008, 130, 5408-+.

17. Deng, X.-M.; Cai, P.; Ye, S.; Sun, X.-L.; Liao, W.-W.; Li, K.; Tang, Y.; Wu, Y.-D.; Dai, L.-X. Enantioselective synthesis of vinylcyclopropanes and vinylepoxides mediated by camphor-derived sulfur ylides: Rationale of enantioselectivity, scope, and limitation. J. Am. Chem. Soc. 2006, 128, 9730-9740.

18. Deng, X.-M.; Sun, X. L.; Tang, Y. Highly regioselective rearrangement of 2-substituted vinylepoxides catalyzed by gallium(III) triflate. J. Org. Chem. 2005, 70, 6537-6540.

Patents

1. Small molecule   myristate inhibitors of bcr-abl and methods of use. Gray, N. S.; Zhang, J.; Okram, B.; Deng, X.; Chang, J.; Wojciechowski, A. PCT Int. Appl. WO  2009073153;  Chem. Abstr. 2009, 151, 49314.

2. Preparation of pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders. Gray, N. S.; Deng, X.; Kwiatkowski, N. P. PCT Int. Appl. WO2010080712; Chem. Abstr. 2010, 153, 175009.

3.  Indazole compounds and their use. Gray, N. S.; Zhou, W.; Deng, X. PCT Int. Appl. WO2011115725.

厦门大学分子影像暨转化医学研究中心 福建省分子影像诊疗工程技术研究中心 厦门市分子影像工程技术研究中心 版权所有
地址:福建省厦门市翔安区翔安南路厦门大学曾辉楼,邮编:361102
电话:0592-2880646,邮箱:xiamen-cmitm@xmu.edu.cn