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Development of highly potent glucocorticoids for steroid-resistant severe asthma

文献类型：期刊论文

作者He, Yuanzheng1,2; Shi, Jingjing3; Quang Tam Nguyen4; You, Erli3; Liu, Hongbo5; Ren, Xin6; Wu, Zhongshan7; Li, Jianshuang8; Qiu, Wenli6; Khoo, Sok Kean9
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期2019-04-02
卷号116期号:14页码:6932-6937
关键词steroid resistant asthma glucocorticoid high potency VSG158 VSG159
ISSN号0027-8424
DOI10.1073/pnas.1816734116
通讯作者He, Yuanzheng(ajian.he@hit.edu.cn) ; Yi, Wei(yiwei@gzhmu.edu.cn) ; Min, Booki(minb@ccf.org) ; Xu, H. Eric(eric.xu@vai.org)
英文摘要Clinical application of inhaled glucocorticoids (GCs) has been hampered in the case of steroid-resistant severe asthma. To overcome this limitation, we have developed a series of highly potent GCs, including VSGC12, VSG158, and VSG159 based on the structural insight into the glucocorticoid receptor (GR). Particularly, VSG158 exhibits a maximal repression of lung inflammation and is 10 times more potent than the currently most potent clinical GC, Fluticasone Furoate (FF), in a murine model of asthma. More importantly, VSG158 displays a unique property to reduce neutrophilic inflammation in a steroid-resistant airway inflammation model, which is refractory to clinically available GCs, including dexamethasone and FF. VSG158 and VSG159 are able to deliver effective treatments with reduced off-target and side effects. In addition, these GCs also display pharmacokinetic properties that are suitable for the inhalation delivery method for asthma treatment. Taken together, the excellent therapeutic and side-effect profile of these highly potent GCs holds promise for treating steroid-resistant severe asthma.
WOS关键词FLUTICASONE FUROATE/VILANTEROL ; AIRWAY INFLAMMATION ; PHARMACOKINETICS ; THERAPY ; FUROATE ; DESIGN ; CELLS
资助项目American Asthma Foundation ; Proof of Concept Innovation Award from the Van Andel Institute ; National Natural Science Foundation of China[91217311] ; National Natural Science Foundation of China[81502909] ; Van Andel Research Institute ; National Institute of Allergy and Infectious Diseases/NIH Grants[AI125247] ; National Institute of Allergy and Infectious Diseases/NIH Grants[AI121524]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000463069900070
出版者NATL ACAD SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/290144]  
专题中国科学院上海药物研究所
通讯作者He, Yuanzheng; Yi, Wei; Min, Booki; Xu, H. Eric
作者单位1.Harbin Inst Technol, HIT Ctr Life Sci, Lab Receptor Struct & Signaling, Harbin 150001, Heilongjiang, Peoples R China
2.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA
3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Van Andel Res Inst Shanghai Inst Mat Med,Ctr Stru, Shanghai 201203, Peoples R China
4.Cleveland Clin Fdn, Lerner Res Inst, Dept Inflammat & Immun, 9500 Euclid Ave, Cleveland, OH 44195 USA
5.Van Andel Res Inst, Ctr Epigenet, Grand Rapids, MI 49503 USA
6.Univ Calif San Francisco, Dept Med, Lung Biol Ctr, San Francisco, CA 94158 USA
7.Palo Alto Pharmaceut, Dept Res & Dev, Shanghai 201203, Peoples R China
8.Van Andel Res Inst, Lab Skeletal Biol, Grand Rapids, MI 49503 USA
9.Grand Valley State Univ, Dept Cell & Mol Biol, Allendale, MI 49401 USA
10.Guangzhou Med Univ, Sch Pharmaceut Sci, Key Lab Mol Target & Clin Pharmacol, Guangzhou 511436, Guangdong, Peoples R China
推荐引用方式
GB/T 7714		 He, Yuanzheng,Shi, Jingjing,Quang Tam Nguyen,et al. Development of highly potent glucocorticoids for steroid-resistant severe asthma[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2019,116(14):6932-6937.
APA He, Yuanzheng.,Shi, Jingjing.,Quang Tam Nguyen.,You, Erli.,Liu, Hongbo.,...&Xu, H. Eric.(2019).Development of highly potent glucocorticoids for steroid-resistant severe asthma.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,116(14),6932-6937.
MLA He, Yuanzheng,et al."Development of highly potent glucocorticoids for steroid-resistant severe asthma".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 116.14(2019):6932-6937.

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来源：上海药物研究所

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