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杜冠华

时间:2018/4/17 来源: 阅读:47247次


杜冠华

 

杜冠华,博士,研究员,博士生导师,195612月出生。现任中国医学科学院、北京协和医学院药物研究院副院长,药物筛选中心主任。中华人民共和国国务院政府特殊津贴专家。兼任中国药理学会副理事长;亚洲西太平洋地区药理学家联合会执行委员会委员;中国晶体学会药物晶体学专业委员会名誉主任委员;国家科技重大专项重大新药创制总体专家组专家;中国药典委员会委员;中华医学会中华医学科技奖评审委员;全国仪器分析测试标准化技术委员会委员;中国国际工程咨询公司第一届专家学术委员会专家;中国信息推进联盟医药专业委员会常务副主任委员;中国科学技术协会第八次全国代表大会全国委员会委员等职务。

1978—1982 年毕业于山东医科大学药学院,获学士学位。1986—1989 年毕业于同济医科大学,获医学硕士学位;1992— 1995 年毕业于北京协和医学院,获博士学位。1995—1998 University of Liege, Belgium,博士后,研究神经生物化学。

1998年就职于中国医学科学院北京协和医学院药物研究所,主要从事药物发现、高通量药物筛选、神经和心脑血管药理学的科研和教学工作。主持建立了我国第一个高通量药物筛选体系,包括国内第一个现代化样品库、系列高通量和高内涵药物筛选模型、药学科学数据共享库及生物芯片、生物信息和虚拟筛选等技术,并通过国家科技部验收。基于建立的系列分子、细胞水平高通量药物筛选模型进行大规模药物筛选,发现了一批活性化合物。

以神经血管单元为靶点,研发抗脑缺血新药匹诺塞林,2009年获1.1类化药临床试验批件并转让企业,完成I期临床试验。根据多靶点策略设计筛选出调节中枢神经递质平衡的抗帕金森新药百可利,2011年获1.1类化药临床试验批件,进入临床研究。率先推进我国晶型药物研究,完成新(晶型)尼群地平临床前研究,2011年获临床试验批件。用于治疗糖尿病神经病变的丹酚酸A2016年获1.2类化药临床试验批件。开发治疗脑缺血药注射用丹参多酚酸,已应用于临床。

高通量药物筛选技术体系与应用获得2002年北京市科学技术二等奖和中华医学科技三等奖;新型高通量筛选用蛋白质芯片技术的研究和应用获得2009年北京市科学技术二等奖;天然产物活性评价研究获得2011年中华医学科技奖三等奖等多项奖励;化学药物晶型关键技术体系的建立与应用获得2015年北京市科学技术一等奖和2016年国家科学技术二等奖;药物抗炎与致炎作用评价、机制研究及其应用获得2017年高等学校科学研究科技进步二等奖,曾获全国优秀科技工作者北京市优秀教师等多项荣誉。

长期从事药学科研和教学工作,培养15名博士后、40余名博士和20余名硕士;主编《实验药理学》和《晶型药物》2部研究生教材、《新药研究与评价概论》药学本科生教材,出版专著30余(册)部,发表论文800余篇,申请国际国内专利70余项,获新药临床批件4个。

兼任《中药药理与临床》杂志主编;《Pharmacology & Therapeutics》、《Acta Pharmacologica Sinica》、《医药导报》、《中国药理学通报》、《中国临床药理学与治疗学》副主编;《药学学报》、《中国药理学与毒理学杂志》、《中国药学杂志》、《Marine Drugs》、《基础医学与临床》、《生物信息学》等刊物编委,担任《神经药理学报》第一届编委会顾问委员会主席。

发表文章:

[1]    Wang Jin-Hua*, Li Wan, Zhao Ying, Kang De, Fu Wei-Qi, Zheng Xiang-Jin, Pang Xiao-Cong, Du Guan-Hua*. Members of FOX family could be drug targets of cancers. Pharmacol Ther. 2018; 181: 183-196.

[2]    Wang Jin-Hua*, Li Wan, Zheng Xiang-Jin, Pang Xiao-Cong, Du Guan-Hua*. Research progress on the forkhead box C1. Oncotarget. 2018; 9(15): 12471-12478.

[3]    Zhang Wen, Song Jun-Ke, Zhang Xue, Zhou Qi-Meng, He Guo-Rong, Xu Xiao-Na, Yan Rong, Zhou Wen-Xia, Du Guan-Hua*. Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation. Chin J Nat Med. 2018 Mar; 16(3):184-193.

[4]    Qin Zhi-Zhen, Wang Shou-Bao, Lin Yi-Huang, Zhao Ying, Yang Sheng-Qian, Song Jun-ke, Xie Tao, Tian Jin-long, Wu Song, Du Guan-Hua*. Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice. Acta Pharmaceutica Sinica B, 2018 Mar; 8(2): 306-315.

[5]    Kang De, Pang Xiao-Cong, Lian Wen-Wen, Xu Lv-Jie, Wang Jin-Hua, Jia Hao, Zhang Bao-Yue, Liu Ai-Lin*, Du Guan-Hua*. Discovery of VEGFR2 inhibitors by integrating naïve Bayesian classification, molecular docking and drug screening approaches. RSC Adv, 2018, 8, 5286-5297.

[6]    Pang Xiao-Cong, Kang De, Fang Jian-Song, Zhao Ying, Xu Lv-Jie, Lian Wen-Wen, Liu Ai-Lin*, Du Guan-Hua*. Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer's disease. Chin J Nat Med. 2018 Jan; 16(1): 53-62.

[7]    Cheng Xiao, Yang Ying-Lin, Yang Huan, Wang Yue-Hua*, Du Guan-Hua*. Kaempferol alleviates LPS-induced neuroinflammation and BBB dysfunction in mice via inhibiting HMGB1 release and down-regulating TLR4/MyD88 pathway. Int Immunopharmacol. 2018 Mar; 56:29-35.

[8]    Hou Bi-Yu, Qiang Gui-Fen, Zhao Yue-Rong, Yang Xiu-Ying, Chen Xi, Yan Yu, Wang Xiao-Bo, Liu Chenge, Zhang Li*, Du Guan-Hua*. Salvianolic acid A protects against diabetic nephropathy through ameliorating glomerular endothelial dysfunction via inhibiting AGE-RAGE signaling. Cell Physiol Biochem. 2017; 44:2378-2394.

[9]    Yang Huan, Cheng Xiao, Yang Ying-Lin, Wang Yue-Hua*, Du Guan-Hua*. Ramulus Cinnamomi extract attenuates neuroinflammatory responses via downregulating TLR4/MyD88 signaling pathway in BV2 cells. Neural Regen Res, 2017, 12(11): 1860-1864.

[10] Yuan Tian-Yi, Chen Yu-Cai, Zhang Hui-Fang, Fang Lian-hua*, Du Guan-hua*. Salvianolic acid A, a component of Salvia Miltiorrhiza, attenuates endothelial-mesenchymal transition of HPAECs induced by hypoxia. Am J Chin Med, 2017; 45(6): 1185-1200.

[11] Chen Yu-Cai, Yuan Tian-Yi, Zhang Hui-Fang, Yan Yu, Wang Dan-Shu, Fang Lian-Hua*, Lu Yang, Du Guan-Hua*. Activation of Nrf2 attenuates pulmonary vascular remodeling via inhibiting endothelial-to-mesenchymal transition: An insight from a plant polyphenol. Int J Biol Sci, 2017 Sep, 13(8): 1067-1081.

[12] Pang Xiao-Cong, Fu Hui, Yang Shi-Lun, Wang Lin, Liu Ai-Lin*, Wu Song*, Du Guan-Hua*. Evaluation of novel dual acetyl- and butyrylcholinesterase inhibitors as potential anti-Alzheimer's disease agents using pharmacophore, 3D-QSAR, and molecular docking approaches. Molecules. 2017 Jul 26; 22(8).

[13] Zhang Xue, Du Li-Da, Zhang Wen, Yang Yu-Lin, Zhou Qi-Meng, Du Guan-Hua*. Therapeutic effects of baicalein on rotenone-induced Parkinson's disease through protecting mitochondrial function and biogenesis. Sci Rep. 2017 Aug, 7(1):9968.

[14] Yuan Tian-Yi, Zhang Hui-Fang, Chen Yu-Cai, Jiao Xiao-Zhen, Xie Ping, Fang Lian-hua*, Du Guan-hua*. The Protective Effect of DL0805 derivatives on pulmonary artery cells and the underlying mechanisms study. Current Vasc Pharmacol. 2017 Feb: 15(5): 469-476.

[15] Pang Xiao-Cong, Wang Lin, Kang De, Zhao Ying, Wu Song, Liu Ai-Lin*, Du Guan-Hua*. Effects of P-Glycoprotein on the Transport of DL0410, a Potential Multifunctional Anti-Alzheimer Agent. Molecules. 2017 Jul; 22(8).

[16] Zhang Xue, Yang Yv, Du Li-Da, Zhang Wen, Du Guan-Hua*. Baicalein exerts anti-neuroinflammatory effects to protect against rotenone-induced brain injury in rats. Int Immunopharmacol. 2017 Jun; 50:38-47.

[17] Wang Lin, Pang Xiao-Cong, Yu Zi-Ru, Yang Sheng-Qian, Liu Ai-Lin, Wang Jin-Hua*, Du Guan-Hua*. Actinomycin D synergistically enhances the cytotoxicity of CDDP on KB cells by activating P53 via decreasing P53-MDM2 complex. J Asian Nat Prod Res. 2017 Jun; 19(6): 630-643.

[18] Lian Wen-Wen, Fang Jian-Song, Xu Lv-Jie, Zhou Wei, Kang De, Xiong Wan-Di, Jia Hao, Liu Ai-Lin*, Du Guan-Hua*. DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice. Molecules. 2017 Mar; 22(3). 410. doi: 10.3390/ molecules 22030410.

[19] Yang Sheng-Qian, Yu Zi-Ru, Wang Lin, Yuan Tian-Yi, Wang Xue, Zhang Xue, Wang Jin-Hua, Lv Yang, Du Guan-hua*. The natural product bergenin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting NF-kappa B activition. J Ethnopharmacol. 2017 Mar, 200:147-155.

[20] Wang Jin-hua*, Xu Ya-li, Li Li, Wang Lin, Yao Ru, Sun Qiang, Du Guan-hua*. FOXC1 is associated with estrogen receptor alpha and affects sensitivity of tamoxifen treatment in breast cancer. Cancer Med. 2017 Jan; 6(1): 275-287.

[21] Yan Yu, Zhang Hui-fang, Zhang Zhi-hui, Song Jun-ke, Chen Yu-cai, Wang Xiao-bo, He Yang-yang, Qin Hai-lin, Fang Lian-hua*, Du Guan-hua*. Pharmacokinetics and tissue distribution of coptisine in rats after oral administration by liquid chromatography-mass spectrometry. Biomed Chromatogr. Biomed Chromatogr. 2017 Jul; 31(7). e3918.

[22] Lin Yi-Huang, Yan Yu, Zhang Hui-Fang, Chen Yu-Cai, He Yang-Yang Wang Shou-Bao, Fang Lian-Hua*, Lu Yang, Du Guan-Hua*. Salvianolic acid A alleviates renal injury against the systemic lupus erythematosus induced by pristane in BALB/c mice. Acta Pharm Sin B. 2017 Mar; 7(2): 159-166.

[23] He Yang-yang, Yan Yu, Zhang Hui-fang, Lin Yi-huang, Chen Yu-cai, Yan Yi, Wu ping, Fang Jian-song, Yang Sheng-qian, Yang Shu-hui, Du Guanhua*. Methyl salicylate 2-O-β-d-lactoside alleviates the pathological progression of pristane-induced systemic lupus erythematosus-like disease in mice via suppression of inflammatory response and signal transduction. Drug Des Devel Ther. 2016 Sep; 10:3183-3196.

[24] Yang Sheng-qian, Yu Zhi-ru, Yuan Tian-yi, Wang Lin, Wang Xue, Yang Hai-guang, Sun Lan, Wang Yue-hua, Du Guan-hua*. Therapeutic effect of methyl salicylate 2-O-β-d-lactoside on LPS-induced acute lung injury by inhibiting TAK1/NF-kappaB phosphorylation and NLRP3 expression. Int Immunopharmacol. 2016 Sep; 40: 219-228.

[25] Wang Jin-Hua, Li Li, Liu Shi-Wei, Zhao Ying, Wang Lin, Du Guan-Hua*. FOXC1 promotes melanoma by activating MST1R/PI3K/AKT. Oncotarget. 2016 Aug 11. doi: 10.18632/oncotarget.11224.

[26] Zhou Dan, Zhou Wei, Song Jun-Ke, Feng Zhang-Ying, Yang Ran-Yao, Wu Song, Wang Lin, Liu Ai-Lin*, Du Guan-Hua*. DL0410, a novel dual cholinesterase inhibitor, protects mouse brains against Aβ-induced neuronal damage via the Akt/JNK signaling pathway. Acta Pharmacol Sin. 2016 Nov; 37(11):1401-1412.

[27] Wu Ping, Yan Yu, Ma Lin-lin, Hou Bi-yu, He Yang-yang, Zhang Li, Niu Zi-ran, Song Jun-ke, Pang Xiao-Cong, Yang Xiu-Ying, Du Guan-hua. Effects of the Nrf2 modulator salvianolic acid A alone or combined with metformin on diabetes-associated macrovascular and renal injury. J Biol Chem. 2016 Oct; 291(42): 22288-22301.

[28] Chen Yu-cai, Yuan Tian-yi, Zhang Hui-fang, Wang Dan-shu, Niu Zi-ran, Li Li, Fang Lian-hua*, Du Guan-hua*. Fasudil evokes vasodilatation of rat mesenteric vascular bed via Ca2+ channels and Rho/ROCK pathway. Eur J Pharmacol. 2016, Oct; 788: 226-233.

[29] Sun Lan*, Bai Yong-Yi, Zhao Rui, Sun Tao, Cao Rui-Hua, Wang Fu-yu, He Guo-Rong, Zhang Wen, Chen Ying, Ye Ping*, Du Guan-hua*. Oncological miR-182-3p, a novel smooth muscle cell phenotype modulator, evidences from model rats and patients. Arterioscler Thromb Vasc Biol. 2016, 36(7): 1386-1397.

[30] Chen Yu-cai, Yuan Tian-yi, Zhang Hui-fang, Wang Dan-shu, Yan Yu, Niu Zi-ran, Lin Yi-huang, Fang Lian-hua*, Du Guan-hua*. Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model. Acta Pharmacol Sin. 2016, 37(6): 772-778. (2015 IF 3.166)

[31] Yu Xiao-yan, Zhang Li, Yang Xiu-ying, Li Xiao-ting, Du Guan-hua*. Salvianolic acid A improves the intestinal motility in diabetic rats through antioxidant capacity and up-regulation of nNOS. J Dig Dis. 2016 Jul; 17(7): 441-447.

[32] Wang Shou-bao, Wang Zhen-zhong, Fan Qi-ru, Guo Jing, Gina Galli, Du Guan-hua*, Wang Xin*, Xiao Wei*. Ginkgolide K protects the heart against ER stress injury by activating the IRE1α/XBP1 pathway. Br J Pharmacol. 2016 Aug; 173(15): 2402-2418.

[33] Du Guan-hua*, Sun Lan, Zhao Rui, Du Li-da, Song Jun-ke, Zhang Li, He Guo-rong, Zhang Yong-xiang, Zhang Jun-tian. Polyphenols: Potential source of drugs for the treatment of ischaemic heart disease. Pharmacol Ther. 2016 Jun; 162: 23-34.

[34] Du Guan-hua*, Yuan Tian-yi, Du Li-da, Zhang Yong-xiang*. Pharmacological Mechanisms and the Modulation of Pain. Adv Pharmacol. 2016, 75: 325-361.

[35] Zhao Ying, Mu Xin, Du Guan-hua*. Microtubule-stabilizing agents: New drug discovery and cancer therapy. Pharmacol Ther. 2016 Jun; 162:134-143.

[36] Ma Yin-zhong, Li Li, Niu Zi-ran, Song Jun-ke, Lin Yi-huang, Zhang Hui-fang, Du Guan-hua*. Effect of recombinant plasminogen activator timing on thrombolysis in a novel rat embolic stroke model. Pharmacol Res. 2016 Mar; 107: 291-299.

[37] Yuan Tian-yi, Chen Yu-cai, Zhang Hui-fang, Li Li, Jiao Xiao-zhen, Xie Ping, Fang Lian-hua*, Du Guan-hua*. DL0805-2, a novel indazole derivative, relaxes Angiotensin II-induced contractions of rat aortic rings by inhibiting Rho kinase and calcium fluxes. Acta Pharmacol Sin. 2016, 37(5): 604-616.

[38] Sun Lan, Zhao Rui, Zhang Li, Zhang Wei-Ku, He Guo-Rong, Yang Sheng-Qian, Song Jun-Ke, Du Guan-hua*. Prevention of vascular smooth muscle cell proliferation and injury-induced neointimal hyperplasia by CREB-mediated p21 induction: An insight from a plant polyphenol. Biochem Pharmacol. 2016, 103: 40-52.

[39] Song Jun-ke, Zhang Wen, Sun Jia-lin, Zhang Xue, Xu Xiao-na, Zhang Li, Feng Zhang-ying, Du Guan-hua*. Determination of salvianolic acid C in rat plasma using liquid chromatography-mass spectrometry and its application to pharmacokinetic study. Biomed Chromatogr. 2016 Mar; 30(3): 376-383.

[40] Zhao Rui, Wang Shou-bao, Huang Zhong-Lin, Zhang Li, Yang Xiu-Ying, Bai Xiao-Yu, Zhou Dan, Qin Zhi-Zhen, Du Guan-Hua*. Lipopolysaccharide-induced serotonin transporter up-regulation involves PKG-I and p38MAPK activation partially through A3 adenosine receptor. Biosci Trends. 2015, 9(6):367-376.

[41] Fang Jian-Song, Pang Xiao-cong, Wu Ping, Yan Rong, Gao Li, Li Chao, Lian Wen-Wen, Wang Qi, Liu Ai-Lin*, Du Guan-Hua*. Molecular modeling on berberine derivatives toward BuChE: An integrated study with QSAR models, molecular docking, and molecular dynamics simulations. Chem Biol Drug Des. 2016 May; 87(5): 649-663.

[42] Fang Jian-song, Pang Xiao-cong, Yan Rong, Lian Wen-wen, Li Chao, Wang Qi, Liu Ai-Lin*, Du Guan-Hua*. Discovery of neuroprotective compounds by machine learning approaches. RSC Adv. 2016, 6, 9857-9871.

[43] Li Chao, Song Xiao-wei, Song Jnu-Ke, Pang Xiao-Cong, Wang Zhe, Zhao Ying, Lian Wen-Wen, Liu Ai-Lin*, Du Guan-Hua*. Pharmacokinetic study of gallocatechin-7-gallate from Pithecellobium clypearia Benth. in rats. Acta Pharm Sin B. 2016 Jan; 6(1):64-70.

[44] Mu Xin, Yuan Xia, Du Li-da, He Guo-rong, Du Guan hua*. Antagonism of quercetin against tremor induced by unilateral striatal lesion of 6-OHDA in rats. J Asian Nat Prod Res. 2016 Jan; 18(1):65-71.

 

近三年学术获奖:

[1]    2016 年度国家科学技术奖二等奖,“化学药物晶型关键技术体系的建立与应用”,第一完成人。

[2]    2014年北京市科学技术奖壹等奖,“化学药物晶型关键技术体系的建立与应用,第一完成人。

[3]    2017年中华医学科技奖叁等奖,“天然产物成药性评价技术创新及应用”,第一完成人。

[4]    2017年高等学校科学研究科技进步二等奖,药物抗炎与致炎作用评价、机制研究及其应用,第二完成人。

 

 

 

 

 

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