Discovery of a highly potent glucocorticoid for asthma treatment
文献类型：期刊论文
| 作者 | He, Yuanzheng4; Shi, Jingjing3 ; Yi, Wei3; Ren, Xin2; Gao, Xiang4; Li, Jianshuang1,7; Wu, Nanyan2; Weaver, Kevin1; Xie, Qian6; Khoo, Sok Kean5
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| 刊名 | CELL DISCOVERY
 |
| 出版日期 | 2015 |
| 卷号 | 1 |
| 关键词 | Glucocorticoids glucocorticoid receptor VSGC12 potency asthma |
| ISSN号 | 2056-5968 |
| DOI | 10.1038/celldisc.2015.35 |
| 文献子类 | Article |
| 英文摘要 | Glucocorticoids are the most effective treatment for asthma. However, their clinical applications are limited by low efficacy in severe asthma and by undesired side effects associated with high dose or prolonged use. The most successful approach to overcome these limitations has been the development of highly potent glucocorticoids that can be delivered to the lungs by inhalation to achieve local efficacy with minimal systemic effects. On the basis of our previous structural studies, we designed and developed a highly potent glucocorticoid, VSGC12, which showed an improved anti-inflammation activity in both cell-based reporter assays and cytokine inhibition experiments, as well as in a gene expression profiling of mouse macrophage RAW264.7 cells. In a mouse asthma model, VSGC12 delivered a higher efficacy than fluticasone furoate, a leading clinical compound, in many categories including histology and the number of differentiated immune cells. VSGC12 also showed a higher potency than fluticasone furoate in repressing most asthma symptoms. Finally, VSGC12 showed a better side effect profile than fluticasone furoate at their respective effective doses, including better insulin response and less bone loss in an animal model. The excellent therapeutic and side effect properties of VSGC12 provide a promising perspective for developing this potent glucocorticoid as a new effective drug for asthma. |
| 资助项目 | NIDDK/NIH fund[DK066202] ; NIDDK/NIH fund[DK071662] ; American Asthma Foundation fund[00000000] ; Proof of Concept Innovation Award, Amway (China)[00000000] ; National Natural Science Foundation of China[NSFC 91217311] ; National Natural Science Foundation of China[NSFC 81502909] ; Van Andel Research Institute[00000000] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000414776800035 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276791]  |
| 专题 | 药物靶标结构与功能中心 |
| 通讯作者 | He, Yuanzheng |
| 作者单位 | 1.Van Andel Res Inst, Lab Skeletal Biol, Grand Rapids, MI USA; 2.Univ Calif San Francisco, Dept Med, Lung Biol Ctr, San Francisco, CA USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Ctr Struct & Funct Drug Targets,VARI SIMM Ctr, Shanghai, Peoples R China; 4.Van Andel Res Inst, Lab Struct Sci, 333 Bostwick Ave Northeast, Grand Rapids, MI 49503 USA; 5.Grand Valley State Univ, Dept Cell & Mol Biol, Grand Rapids, MI USA 6.Van Andel Res Inst, Ctr Canc & Cell Biol, Lab Mol Oncol, Mol Oncogenesis & Targeted Therapy, Grand Rapids, MI USA; 7.Wuhan Univ, Coll Life Sci, Wuhan, Hubei, Peoples R China; |
| 推荐引用方式 GB/T 7714 | He, Yuanzheng,Shi, Jingjing,Yi, Wei,et al. Discovery of a highly potent glucocorticoid for asthma treatment[J]. CELL DISCOVERY,2015,1. |
| APA | He, Yuanzheng.,Shi, Jingjing.,Yi, Wei.,Ren, Xin.,Gao, Xiang.,...&Xu, H. Eric.(2015).Discovery of a highly potent glucocorticoid for asthma treatment.CELL DISCOVERY,1. |
| MLA | He, Yuanzheng,et al."Discovery of a highly potent glucocorticoid for asthma treatment".CELL DISCOVERY 1(2015). |
入库方式： OAI收割
来源：上海药物研究所
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