师资队伍 | 蒋宇扬, PhD

蒋宇扬

教授,博士生导师

蒋宇扬博士1986年毕业于沈阳药科大学,1993年和1996年分别获得中国科学院应用生态研究所硕士和博士学位。1986-1990年任职于沈阳药科大学,1996-1998年,清华大学化学系博士后,师从赵玉芬院士。1998年10月-2004年11月,清华大学化学系副教授、清华大学生命有机磷化学与化学生物学教育部重点实验室常务副主任(2001年3月);2004年11月-至今,清华大学化学系/医学院教授、清华大学深圳研究生院广东省化学生物学重点实验室主任,2010年7-至今,深圳市化学生物学重点实验室--省部共建国家重点实验室培育基地主任,从事肿瘤化学生物学研究工作。 在工作期间,蒋宇扬博士长期从事“一个基因(pokemon)两种疾病(肝癌和乳腺癌)”的肿瘤化学生物学研究,在以pokemon为中心的基因调控网络研究及多靶点抗肿瘤药物研发方面获得了一系列创新性成果,创建并形成了新的基于化学生物学的肿瘤个体化诊疗研究技术平台和理论体系。蒋宇扬博士已授权23项中国专利,发表~220余篇学术论文,并应邀在众多国内外会议,包括The 1st Shenzhen International Biotech Innovation Forum & Exhibition Invitation等会议上做学术报告。蒋宇扬博士是“Protein and Peptide Letters”,“Chinese Chemical Chemistry” 以及 “中国新药杂志”的编委。


研究方向

蒋宇扬课题组的研究方向包括:1)肿瘤诊断检测;2)pokemon信号传导通路研究;3)多靶点高通量药物筛选技术研究及抗肿瘤药物研发;4)肿瘤的代谢组学和蛋白质组学研究;5)基于荧光共轭聚合物的生物分析、细胞成像及药物转运研究
1) 肿瘤诊断检测:肿瘤早期诊断和治疗是提高癌症患者生存率的关键。建立新颖的高通量肿瘤细胞检测技术,开发快速、灵敏、准确的肿瘤检测试剂盒是亟待解决的重大课题之一。针对这些问题,利用可选择性催化剪切DNA 中嵌入的RNA 碱基的荧光标记DNA 酶( RNA-cleaving Fluorescent DNAaymes, RFD)模型,本课题组建立了可特异性识别肿瘤分子的RFD 分子探针检测技术,并将其应用于乳腺癌的体外筛查。我们围绕肿瘤细胞的代谢混合物为研究对象,采用RFD 模型以及指数式富集的配体系统进化(systematic evolution of ligands by exponential Enrichment,SELEX)技术,筛选获得特异分子探针以进行肿瘤细胞及肿瘤亚型细胞的特异性检测,解决个体化用药相关重要生物标志物及其新型检测试剂盒研发关键技术,从而实现肿瘤疾病的早期检测诊断和预警预防。
 
2)pokemon信号传导通路研究:肿瘤功能基因的研究是当今功能基因组研究的热点之一,针对肿瘤功能基因的靶向药物开发,是抗肿瘤药物研究开发的重要方向。Pokemon是BTB-锌指结构蛋白家族成员,在肿瘤的形成过程中起着至关重要的作用,可能成为抗肿瘤新药的一个高效靶标。我们课题组以Pokemon 为切入点,利用功能基因组学和生物信息学等领域的先进技术方法,研究了Pokemon介导的肿瘤细胞信号传导通路,在乳腺癌和肝癌体系中发现了Pokemon 可以直接调控的基因网络,涉及细胞生长、转移、凋亡、细胞周期、多药耐药等多条信号通路及核苷、氨基酸、脂质等多条物质代谢通路。这些将为肿瘤发生的多基因调控网络的研究,以及具有自主知识产权的抗肿瘤药物靶标的选择和组合奠定理论基础。
 
3)多靶点高通量药物筛选技术研究及抗肿瘤药物研发: 肿瘤是多基因调控的疾病,发现高效低毒的新型多靶点药物是抗肿瘤药物研发的重要方向,大范围筛选可显著提高多靶点化合物的命中率并避开专利保护。本实验室与新加坡国立大学联合开发了支持向量机(SVM)多靶点筛选系统,基本可以满足大范围多靶点药物筛选要求。利用该系统,对实验室鉴定的多靶点组合,从PUBCHEM和MDDR数据库中筛选出潜在的多靶点化合物结构,建立了多靶点虚拟化合物库。对筛选出的化合物结构的来源进行分析,基于优秀先导化合物通常有的优秀特征对源于药物多产科的化合物进行进一步的结构修饰,设计并合成了潜在多靶点抗肿瘤活性的化合物库。
 
4)肿瘤的代谢组学和蛋白质组学研究:由于细胞内代谢物和蛋白质的种类繁多,物质性质差异大,采用传统的全分析方法会导致大量的信息丢失,本实验室致力于开发新的代谢和蛋白靶标分析策略,对不同种类的物质分别进行靶标分析,以获得更加全面的代谢物和蛋白质信息。我们的主要研究兴趣是利用各种衍生化手段,对同种代谢物或蛋白质进行衍生化反应,以期提高该类物质的检测灵敏度,并最终将该技术应用于临床样本的分析,对肿瘤标志物的发现提供技术平台。
 
5) 基于荧光共轭聚合物的生物分析、细胞成像及药物转运研究:荧光共轭聚合物及其制备的聚合物纳米颗粒应用于生物传感、细胞成像、细胞内动态变化与生物监测以及协助抗癌药物转运等成为了该领域研究的热点。本研究方向主要是建立有助于肿瘤的信号转导、药物筛选、疾病诊断、药物转运等研究的新型荧光分子探针;通过设计合成功能性荧光共轭聚合物,建立针对不同生物标记物的分析检测方法,以达到疾病的早期诊断及预后评估;重点针对细胞凋亡和细胞自噬过程中的形态学特征和生化特征,建立细胞成像方法,以达到细胞内实时监测生物靶标分子,方便、快捷地分析细胞凋亡及自噬过程,拓展荧光共轭聚合物的生物学应用。

科学贡献

构建了可特异性识别乳腺癌的分子探针,对乳腺癌的早期筛查检测和个体化治疗具有重要的学术意义。在临床上首次发现Pokemon与Survivin协同高表达,与乳腺癌病人生存率呈负相关,对临床治疗具有重要科学指导意义。和新加坡国立大学陈宇综教授合作,建立了基于支持向量机的多靶点高通量虚拟筛选系统,该系统具有高的筛选速度(850 万个化合物/小时)、高靶点选择性(>95.3%)、低假阳性(<0.025%)等显著优势基本可以满足多靶点药物筛选要求。首次通过对上市药物的天然产物类先导化合物的系统的分析,得到了优秀先导化合物通常有的优秀特征以及弱点,以及克服其弱点的有效方法,为鉴别和优化优秀先导化合物提供了指导方法,具有重要的意义。
 

研究成果

 基于RFD探针的肿瘤肿瘤诊断检测:以脱氧核酶适配体分子为基础设计合成了针对肿瘤细胞代谢物的适配体分子探针库,针对乳腺癌MDA-MB-231细胞开展了脱氧核糖适体酶的SELEX筛选工作,筛选获得了多条能够与MDA-MB-231细胞代谢物产生响应的适体酶分子探针,其中部分探针对MDA-MB-231细胞代谢物具有良好的反应特异性及结合能力,而且对临床肿瘤组织也具有较好的识别鉴定作用。


 图1:RFD分子探针对乳腺癌的识别检测。A. 以RFD结构为基础的分子探针检测模型;B. 筛选获得的分子探针对不同乳腺癌细胞的响应;C. 分子探针对临床乳腺癌样品的识别响应;D. 分子探针对临床乳腺癌样品的特异性鉴定(Analysis Chemistry, 2015, 87, 569−577)


pokemon信号传导通路研究:利用临床乳腺癌组织样品分析获得Pokemon的表达与病人的生存期呈显著的负相关,表明Pokemon可以作为预后症状的负标记因子。同时利用组织芯片研究表明,Pokemon和Survivin的表达具有高度协同性,因而可以推断Pokemon与survivin的调控作用对乳腺癌的发生发展有重要作用。进一步利用生物学手段研究表明通过直接作用于survivin的启动子而激活其转录表达,并且这种作用同时抑制了p53对survivin表达的下调作用。

图2. pokemon与survivin在肿瘤临床组织样品中的协同表达关系 (Breast Cancer Research, 2011, 11, R26)
 

多靶点药物的来源分析:建立大的包含整个化学空间的化合物库价格非常昂贵,如果能在相对较小的且成药性强的化学空间进行搜索,则发现成药的化合物的几率将大大提高。哪些类化合物的成药性强呢?多靶点药物结构从哪里来呢?我们对939个上市药,363个临床药以及19721个活性化合物进行分析,80%的上市药主要集中于17个物种科,67%临床药主要集中于30个物种科,说明药物在自然界的分布具有群集现象,即药物集中来源于自然界进化树上的特定的分支上,并阐明了产药分支的分布规律,该成果为药物设计及寻找新的类药母核提供了技术支撑和理论指导。

图3.细菌界及植物界药物多产科分布图,细菌界有289个已知的科,包含24个药物多产科;植物界有740个已知的科,包含66个药物多产科 (National Academy of Sciences of the United States of America, 108, 12943-12948)

优秀化合物鉴别和结构优化方法:通常一个母核结构可衍生出众多的衍生物,如何鉴别及优化优秀先导化合物自然成为成为药物研发领域中另一个关键的问题。我们通过对上市药物的天然产物类先导化合物的系统的分析,得到了优秀先导化合物通常有的优秀特征以及弱点,以及克服其弱点的有效方法,为鉴别和优化优秀先导化合物提供了指导方法。

表1. 2008-2012年FDA批准的源于天然的药物统计数据(Nature biotechnology 2014, 32 (10), 979-80)


 


多肽从头测序及蛋白质的定量研究:建立了以有机磷酸化学为基础的稳定同位素N-磷酰化标记(SIPL)的方法用于肽段的从头测序和蛋白定量。这种新的标记方法操作简便,可以在40min内完成反应并且不需要额外的除盐程序。通过nano LC-chip/TOF MS对蛋白进行定量,发现测量比率和理论比率有非常好的相关性,相对误差在0.5%-6.7%之间,相对标准偏差小于10.6%,表明这种新的方法具有重复性和精确性。基于有机磷酸化学并通过稳定同位素标记的方法为蛋白组学的定量开辟了一条新的路径。
 

图4多肽的磷酰化标记及定量检测(Chemical communications, 2012, 48, 10198-10200)

建立了基于荧光共轭聚合物PPE的针对多种生物大分子标记物的体外分析测试方法:
 


图5 Caspase酶:(ACS Appl. Mater. Interfaces 2012, 4, 405−410);蛋白酶:(J. Mater. Chem. B, 2013, 1, 1402–1405);磷酸水解酶:(ACS Appl. Mater. Interfaces 2012, 4, 3784−3787)
 

建立了针对金属离子检测的基于4种共轭聚合物的sensor array荧光传感阵列方法:

6 (ACS Appl. Mater. Interfaces 2015, 7, 6882−6888)
 


荣誉和奖项

“十一五”国家科技计划执行突出贡献奖(2011年)
国务院政府津贴(2011年)
深圳市政府津贴(2010年)
广东省科学技术奖三等奖(2008年,第一完成人)
深圳市科技创新奖(2008年,第一完成人)
深圳市人才“双百计划”(2008年)
教育部“新世纪优秀人才”支持计划(2007年)
广东省劳动模范(2006年)
代表性论文
 
1. Zhang, W.; Zhang, B.; Zhang, W.; Yang, T.; Wang, N.; Gao, C.; Tan, C.; Liu, H.; Jiang, Y*., Synthesis and antiproliferative activity of 9-benzylamino-6-chloro-2-methoxy-acridine derivatives as potent DNA-binding ligands and topoisomerase II inhibitors. Eur. J. Med. Chem. 2016, 116, 59-70.
2. Wang, Y.; Gao, D.; Chu, B.; Gao, C.; Cao, D.; Liu, H.; Jiang, Y*., Exposure of CCRF-CEM cells to acridone derivative 8a triggers tumor death via multiple mechanisms. Proteomics 2016, 16 (7), 1177-1190.
3. Chen, Y.; Gao, D.; Liu, H.; Lin, S.; Jiang, Y*., Drug cytotoxicity and signaling pathway analysis with three-dimensional tumor spheroids in a microwell-based microfluidic chip for drug screening. Anal. Chim. Acta 2015, 898, 85-92.
4. Mao, Y.; Liu, M.; Tram, K.; Gu, J.; Salena, B. J.; Jiang, Y*..; Li, Y., Optimal DNA Templates for Rolling Circle Amplification Revealed by In Vitro Selection. Chemistry-a European Journal 2015, 21 (22), 8069-8074.
5. Tao, L.; Zhu, F.; Qin, C.; Zhang, C.; Chen, S.; Zhang, P.; Zhang, C.; Tan, C.; Gao, C.; Chen, Z.; Jiang, Y*.; Chen, Y. Z., Clustered Distribution of Natural Product Leads of Drugs in the Chemical Space as Influenced by the Privileged Target-Sites. Scientific Reports 2015, 5.
6. Zhang, B.; Chen, K.; Wang, N.; Gao, C.; Sun, Q.; Li, L.; Chen, Y.; Tan, C.; Liu, H.; Jiang, Y*., Molecular design, synthesis and biological research of novel pyridyl acridones as potent DNA-binding and apoptosis-inducing agents. Eur. J. Med. Chem. 2015, 93, 214-226.
7. Mao, Y.; Chen, Y.; Li, S.; Lin, S.; Jiang, Y*.., A Graphene-Based Biosensing Platform Based on Regulated Release of an Aptameric DNA Biosensor. Sensors (Basel, Switzerland) 2015, 15 (11), 28244-56.
8. Gao, C.; Li, B.; Zhang, B.; Sun, Q.; Li, L.; Li, X.; Chen, C.; Tan, C.; Liu, H.; Jiang, Y*., Synthesis and biological evaluation of benzimidazole acridine derivatives as potential DNA-binding and apoptosis-inducing agents. Bioorg. Med. Chem. 2015, 23 (8), 1800-1807.
9. Li, X.; Gao, C.; Yang, T.; Zhang, B.; Tan, C.; Liu, H.; Jiang, Y*., A POCl3-mediated synthesis of substituted fused azoacridones derivatives. Rsc Advances 2015, 5 (36), 28670-28678.
10. He, S.; Qu, L.; Shen, Z.; Tan, Y.; Zeng, M.; Liu, F.; Jiang, Y*.; Li, Y., Highly Specific Recognition of Breast Tumors by an RNA-Cleaving Fluorogenic DNAzyme Probe. Analytical Chemistry 2015, 87 (1), 569-577.
11. Chu, B.; Liu, F.; Li, L.; Ding, C.; Chen, K.; Sun, Q.; Shen, Z.; Tan, Y.; Tan, C.; Jiang, Y*., A benzimidazole derivative exhibiting antitumor activity blocks EGFR and HER2 activity and upregulates DR5 in breast cancer cells. Cell death & disease 2015, 6, e1686.
12. Chen, K.; Chu, B.-z.; Liu, F.; Li, B.; Gao, C.-m.; Li, L.-l.; Sun, Q.-s.; Shen, Z.-f.; Jiang, Y*., New benzimidazole acridine derivative induces human colon cancer cell apoptosis in vitro via the ROS-JNK signaling pathway. Acta Pharmacologica Sinica 2015, 36 (9), 1074-1084.
13. Gao, F.; Liu, F.; Zheng, J.; Zeng, M.; Jiang, Y*., A Catalytic DNA Probe with Stem-loop Motif for Human T47D Breast Cancer Cells. Analytical Sciences 2015, 31 (8), 815-822.
14. Liu, H.; Li, X.; Liu, F.; Tan, Y.; Jiang, Y*., A simple and novel amide ligand based on quinoline derivative used for palladium-catalyzed Suzuki coupling reaction. Journal Of Organometallic Chemistry 2015, 794, 27-32.
15. Tao, L.; Zhu, F.; Xu, F.; Chen, Z.; Jiang, Y*.; Chen, Y. Z., Co-targeting cancer drug escape pathways confers clinical advantage for multi-target anticancer drugs. Pharmacological Research 2015, 102, 123-131.
16. Qin, C.; Tao, L.; Phang, Y. H.; Zhang, C.; Chen, S. Y.; Zhang, P.; Tan, Y.; Jiang, Y*.; Chen, Y. Z., The Assessment of the Readiness of Molecular Biomarker-Based Mobile Health Technologies for Healthcare Applications. Scientific Reports 2015, 5.
17. Tao, L.; Zhu, F.; Qin, C.; Zhang, C.; Xu, F.; Tan, C. Y.; Jiang, Y*.; Chen, Y. Z., Nature's contribution to today's pharmacopeia. Nature biotechnology 2014, 32 (10), 979-80.
18. Zhang, B.; Li, X.; Li, B.; Gao, C.; Jiang, Y*., Acridine and its derivatives: a patent review (2009-2013). Expert Opinion on Therapeutic Patents 2014, 24 (6), 647-664.
19. Xin, T.; Zhang, C.; Tan, C.; Jiang, Y*., Biological Evaluation and Structure Modification of (S)-3-Aminopyrrolidine Derivatives. Chemical Research in Chinese Universities 2014, 30 (1), 91-97.
20. Wu, Q.; Gao, D.; Wei, J.; Jin, F.; Xie, W.; Jiang, Y*.; Liu, H., Development of a novel multi-layer microfluidic device towards characterization of drug metabolism and cytotoxicity for drug screening. Chemical Communications 2014, 50 (21), 2762-2764.
21. Li, B.; Gao, C.-M.; Sun, Q.-S.; Li, L.-L.; Tan, C.-Y.; Liu, H.-X.; Jiang, Y*., Novel synthetic acridine-based derivatives as topoisomerase I inhibitors. Chin. Chem. Lett. 2014, 25 (7), 1021-1024.
22. Gao, D.; Jin, F.; Liu, H.; Wang, Y.; Jiang, Y*., Metabonomic study on the antitumor effect of flavonoid derivative 3d in HepG2 cells and its action mechanism. Talanta 2014, 118, 382-388.
23. Chen, X.; Gao, D.; Liu, F.; Gao, X.; Wang, S.; Zhao, Y.; Liu, H.; Jiang, Y*., A novel quantification method for analysis of twenty natural amino acids in human serum based on N-phosphorylation labeling using reversed-phase liquid chromatography-tandem mass spectrometry. Anal. Chim. Acta 2014, 836, 61-71.
24. Ding, C.; Zhang, C. L.; Zhang, M. L.; Chen, Y. Z.; Tan, C. Y.; Tan, Y.; Jiang, Y*., Multitarget inhibitors derived from crosstalk mechanism involving VEGFR2. Future Med Chem 2014, 6 (16), 1771-1789.
25. Qu, L.; Ali, M. M.; Aguirre, S. D.; Liu, H.; Jiang, Y*.; Li, Y., Examination of Bacterial Inhibition Using a Catalytic DNA. PLoS One 2014, 9 (12).
26. Chen, Z.; Liu, F.; Zhang, N.; Cao, D.; Liu, M.; Tan, Y.; Jiang, Y*., p38 beta, A Novel Regulatory Target of Pokemon in Hepatic Cells. Int. J. Mol. Sci. 2013, 14 (7), 13511-13524.
27. Jin, F.; Gao, D.; Wu, Q.; Liu, F.; Chen, Y.; Tan, C.; Jiang, Y*., Exploration of N-(2-aminoethyl)piperidine-4-carboxamide as a potential scaffold for development of VEGFR-2, ERK-2 and Abl-1 multikinase inhibitor. Bioorg. Med. Chem. 2013, 21 (18), 5694-5706.
28. Jin, F.; Gao, D.; Zhang, C.; Liu, F.; Chu, B.; Chen, Y.; Chen, Y. Z.; Tan, C.; Jiang, Y*., Exploration of 1-(3-chloro-4-(4-oxo-4H-chromen-2-yl)phenyl)-3-phenylurea derivatives as selective dual inhibitors of Raf1 and JNK1 kinases for anti-tumor treatment. Bioorg. Med. Chem. 2013, 21 (3), 824-831.
29. Jin, X. L.; Sun, Q. S.; Liu, F.; Yang, H. W.; Liu, M.; Liu, H. X.; Xu, W.; Jiang, Y*., microRNA 21‐mediated suppression of Sprouty1 by Pokemon affects liver cancer cell growth and proliferation. Journal of Cellular Biochemistry 2013, 114, 1625-1633.
30. Lang, X.; Li, L.; Chen, Y.; Sun, Q.; Wu, Q.; Liu, F.; Tan, C.; Liu, H.; Gao, C.; Jiang, Y*., Novel synthetic acridine derivatives as potent DNA-binding and apoptosis-inducing antitumor agents. Bioorg. Med. Chem. 2013, 21 (14), 4170-4177.
31. Lang, X.-L.; Sun, Q.-S.; Chen, Y.-Z.; Li, L.-L.; Tan, C.-Y.; Liu, H.-X.; Gao, C.-M.; Jiang, Y*., Novel synthetic 9-benzyloxyacridine analogue as both tyrosine kinase and topoisomerase I inhibitor. Chin. Chem. Lett. 2013, 24 (8), 677-680.
32. Liu, R.; Tan, Y.; Zhang, C.; Wu, J.; Mei, L.; Jiang, Y*.; Tan, C., A real-time fluorescence turn-on assay for trypsin based on a conjugated polyelectrolyte. Journal of Materials Chemistry B 2013, 1 (10), 1402-1405.
33. Wu, J.; Tan, Y.; Xie, Y.; Wu, Y.; Zhao, R.; Jiang, Y*.; Tan, C., Diazobenzene-containing conjugated polymers as dark quenchers. Chemical Communications 2013, 49 (97), 11379-11381.
34. Zhang, N.-N.; Sun, Q.-S.; Chen, Z.; Liu, F.; Jiang, Y*., Homeostatic regulatory role of Pokemon in NF-kappa B signaling: stimulating both p65 and I kappa B alpha expression in human hepatocellular carcinoma cells. Molecular and Cellular Biochemistry 2013, 372 (1-2), 57-64.
35. Gao, D.; Liu, H.; Lin, J.-M.; Wang, Y.; Jiang, Y*., Characterization of drug permeability in Caco-2 monolayers by mass spectrometry on a membrane-based microfluidic device. Lab on a Chip 2013, 13 (5), 978-985.
36. Wang, Y.; Gao, D.; Chen, Z.; Li, S.; Gao, C.; Cao, D.; Liu, F.; Liu, H.; Jiang, Y*., Acridone Derivative 8a Induces Oxidative Stress-Mediated Apoptosis in CCRF-CEM Leukemia Cells: Application of Metabolomics in Mechanistic Studies of Antitumor Agents. Plos One 2013, 8 (5), e63572.
37. Gao, C. M.; Li, S. F.; Lang, X. L.; Liu, H. X.; Liu, F.; Tan, C. Y.; Jiang, Y*., Synthesis and evaluation of 10-(3,5-dimethoxy)benzyl-9(10H)-acridone derivatives as selective telomeric G-quadruplex DNA ligands. Tetrahedron 2012, 68 (38), 7920-7925.
38. Gao, X.; Wu, H.; Lee, K.-C.; Liu, H.; Zhao, Y.; Cai, Z.; Jiang, Y*., Stable Isotope N-Phosphorylation Labeling for Peptide de Novo Sequencing and Protein Quantification Based on Organic Phosphorus Chemistry. Analytical chemistry 2012, 84 (23), 10236-10244.
39. Han, B. C.; Ma, X. H.; Zhao, R. Y.; Zhang, J. X.; Wei, X. N.; Liu, X. H.; Liu, X.; Zhang, C. L.; Tan, C. Y.; Jiang, Y*.; Chen, Y. Z., Development and experimental test of support vector machines virtual screening method for searching Src inhibitors from large compound libraries. Chem Cent J 2012, 6.
40. Jin, F.; Zhang, N.; Tan, C.; Gao, D.; Zhang, C.; Liu, F.; Chen, Z.; Gao, C.; Liu, H.; Li, S.; Jiang, Y*., 2'-Chloro-4'-aminoflavone Derivatives Selectively Targeting Hepatocarcinoma Cells: Convenient Synthetic Process, G2/M Cell Cycle Arrest and Apoptosis Triggers. Archiv Der Pharmazie 2012, 345 (7), 525-534.
41. Jin, Y. B.; Luan, X. D.; Liu, H. X.; Gao, C. M.; Li, S. F.; Cao, D. L.; Li, X. Y.; Cai, Z. W.; Jiang, Y*., Pharmacokinetics and metabolite identification of a novel VEGFR-2 and Src dual inhibitor 6-chloro-2-methoxy-N-(2-methoxybenzyl) acridin-9-amine in rats by liquid chromatography tandem mass spectrometry. Talanta 2012, 89, 70-76.
42. Zhu, F.; Ma, X. H.; Qin, C.; Tao, L.; Liu, X.; Shi, Z.; Zhang, C. L.; Tan, C. Y.; Chen, Y. Z.; Jiang, Y*., Drug Discovery Prospect from Untapped Species: Indications from Approved Natural Product Drugs. Plos One 2012, 7 (7).
43. Zhao, R.; Xie, Y. H.; Tan, Y.; Tan, C. Y.; Jiang, Y*., Binding of a bcl-2 Family Inhibitor to Bovine Serum Albumin: Fluorescence Quenching and Molecular Docking Study. Protein and Peptide Letters 2012, 19 (9), 949-954.
44. Zhang, X.; Tan, Y.; Zhao, R.; Chu, B.; Tan, C.; Jiang, Y*., Site-directed Mutagenesis Study of the Ile140 in Conserved Hydrophobic Core of Bcl-x(L). Protein and Peptide Letters 2012, 19 (9), 991-996.
45. Zhang, J. X.; Han, B. C.; Wei, X. N.; Tan, C. Y.; Chen, Y. Z.; Jiang, Y*., A Two-Step Target Binding and Selectivity Support Vector Machines Approach for Virtual Screening of Dopamine Receptor Subtype-Selective Ligands. Plos One 2012, 7 (6).
46. Zhang, J.; Jia, J.; Zhu, F.; Ma, X.; Han, B.; Wei, X.; Tan, C.; Jiang, Y*.; Chen, Y., Analysis of bypass signaling in EGFR pathway and profiling of bypass genes for predicting response to anticancer EGFR tyrosine kinase inhibitors. Molecular bioSystems 2012, 8 (10), 2645-56.
47. Zhang, C. L.; Tan, C. Y.; Ding, H. W.; Xin, T.; Jiang, Y*., Selective VEGFR Inhibitors for Anticancer Therapeutics in Clinical Use and Clinical Trials. Current Pharmaceutical Design 2012, 18 (20), 2921-2935.
48. Yang, X. F.; Zu, X. Y.; Tang, J.; Xiong, W.; Zhang, Y.; Liu, F.; Jiang, Y*., Zbtb7 suppresses the expression of CDK2 and E2F4 in liver cancer cells: Implications for the role of Zbtb7 in cell cycle regulation. Molecular Medicine Reports 2012, 5 (6), 1475-1480.
49. Xie, Y. H.; Zhao, R.; Tan, Y.; Zhang, X.; Liu, F.; Jiang, Y*.; Tan, C. Y., Conjugated Polymer-Based Real-Time Fluorescence Caspase Assays. ACS Applied Materials & Interfaces 2012, 4 (1), 405-410.
50. Xie, Y. H.; Tan, Y.; Liu, R. X.; Zhao, R.; Tan, C. Y.; Jiang, Y*., Continuous and Sensitive Acid Phosphatase Assay Based on a Conjugated Polyelectrolyte. ACS Applied Materials & Interfaces 2012, 4 (8), 3784-3787.
51. Tian, J.; Jiang, Y*., Insulin upregulates the expression of zinc finger and BTB domain-containing 7A in HepG2 cells. Molecular Medicine Reports 2012, 6 (6), 1379-1384.
52. Tan, Y.; Zhang, X.; Xie, Y. H.; Zhao, R.; Tan, C. Y.; Jiang, Y*., Label-free fluorescent assays based on aptamer-target recognition. Analyst 2012, 137 (10), 2309-2312.
53. Liu, K.; Liu, F.; Zhang, N. N.; Liu, S. Y.; Jiang, Y*., Pokemon Silencing Leads to Bim-Mediated Anoikis of Human Hepatoma Cell QGY7703. Int. J. Mol. Sci. 2012, 13 (5), 5818-5831.
54. Lin, J. S.; Liu, F.; Jiang, Y*., Antisense Technologies Targeting Fatty Acid Synthetic Enzymes. Recent Patents on Anti-Cancer Drug Discovery 2012, 7 (2), 198-206.
55. Lin, J.; Jin, X.; Bu, Y.; Cao, D.; Zhang, N.; Li, S.; Sun, Q.; Tan, C.; Gao, C.; Jiang, Y*., Efficient synthesis of RITA and its analogues: derivation of analogues with improved antiproliferative activity via modulation of p53/miR-34a pathway. Organic & Biomolecular Chemistry 2012, 10 (48), 9734-9746.
56. Lang, X. L.; Luan, X. D.; Gao, C. M.; Jiang, Y*., Recent Progress of Acridine Derivatives with Antitumor Activity. Progress in Chemistry 2012, 24 (8), 1497-1505.
57. Zu, X.; Ma, J.; Liu, H.; Liu, F.; Tan, C.; Yu, L.; Wang, J.; Xie, Z.; Cao, D.; Jiang, Y*., Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression. Breast Cancer Res. 2011, 13, R26.
58. Zhu, F.; Qin, C.; Tao, L.; Liu, X.; Shi, Z.; Ma, X.; Jia, J.; Tan, Y.; Cui, C.; Lin, J.; Tan, C.; Jiang, Y*.; Chen, Y., Clustered patterns of species origins of nature-derived drugs and clues for future bioprospecting. Proc. Natl. Acad. Sci. U. S. A. 2011, 108 (31), 12943-12948, S12943/1-S12943/139.
59. Zhao, R.; Tan, C.; Xie, Y.; Gao, C.; Liu, H.; Jiang, Y*., One step synthesis of azo compounds from nitroaromatics and anilines. Tetrahedron Lett. 2011, 52 (29), 3805-3809.
60. Zhang, Y.; Zu, X. Y.; Luo, W. S.; Tang, S. S.; Jiang, Y*., siRNA Induced CyclinB1 Knockdown Sensitizes HepG2 Cells to Daunorubicin. Prog. Biochem. Biophys. 2011, 38 (6), 551-557.
61. Zhang, D.; Liu, H.; Zhang, S.; Chen, X.; Li, S.; Zhang, C.; Hu, X.; Bi, K.; Chen, X.; Jiang, Y*., An effective method for de novo peptide sequencing based on phosphorylation strategy and mass spectrometry. Talanta 2011, 84 (3), 614-622.
62. Zhang, C.; Zhai, X.; Wan, F.; Gong, P.; Jiang, Y*., 2-Chloro-1- 4-(2-fluorobenzyl)piperazin-1-yl ethanone. Acta Crystallographica Section E-Structure Reports Online 2011, 67, O708-U2523.
63. Zhang, C.; Tan, C.; Zu, X.; Zhai, X.; Liu, F.; Chu, B.; Ma, X.; Chen, Y.; Gong, P.; Jiang, Y*., Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors. Eur. J. Med. Chem. 2011, 46 (4), 1404-1414.
64. Luan, X.; Gao, C.; Zhang, N.; Chen, Y.; Sun, Q.; Tan, C.; Liu, H.; Jin, Y.; Jiang, Y*., Exploration of acridine scaffold as a potentially interesting scaffold for discovering novel multi-target VEGFR-2 and Src kinase inhibitors. Bioorg. Med. Chem. 2011, 19 (11), 3312-3319.
65. Luan, X.; Gao, C.; Sun, Q.; Tan, C.; Liu, H.; Jin, Y.; Jiang, Y*., Novel synthetic azaacridine analogues as topoisomerase 1 inhibitors. Chem. Lett. 2011, 40 (7), 728-729.
66. Li, Y.; Tan, C.; Gao, C.; Zhang, C.; Luan, X.; Chen, X.; Liu, H.; Chen, Y.; Jiang, Y*., Discovery of benzimidazole derivatives as novel multi-target EGFR, VEGFR-2 and PDGFR kinase inhibitors. Bioorg. Med. Chem. 2011, 19 (15), 4529-4535.
67. Li, S.; Liu, H.; Jin, Y.; Lin, S.; Cai, Z.; Jiang, Y*., Metabolomics study of alcohol-induced liver injury and hepatocellular carcinoma xenografts in mice. J. Chromatogr., B: Anal. Technol. Biomed. Life Sci. 2011, 879 (24), 2369-2375.
68. Hu, X.; Gao, C.; Tan, C.; Zhang, C.; Zhang, H.; Li, S.; Liu, H.; Jiang, Y*., Design and Synthesis of N-phosphoryl Peptide Modified Podophyllotoxin Derivatives as Potent Anticancer Agents. Protein and Peptide Letters 2011, 18 (12), 1258-1264.
69. Chen, X. W.; Liu, H. X.; Jin, Y. B.; Li, S. F.; Bi, X.; Chung, S.; Zhang, S. S.; Jiang, Y*., Separation, identification and quantification of tetrodotoxin and its analogs by LC-MS without calibration of individual analogs. Toxicon 2011, 57 (6), 938-943.