| Title |
Identification of known drugs targeting the endoplasmic reticulum stress response
|
|---|---|
| Published in |
Analytical & Bioanalytical Chemistry, April 2015
|
| DOI | 10.1007/s00216-015-8694-2 |
| Pubmed ID | |
| Authors |
Kun Bi, Kana Nishihara, Thomas Machleidt, Spencer Hermanson, Jun Wang, Srilatha Sakamuru, Ruili Huang, Menghang Xia |
| Abstract |
The endoplasmic reticulum (ER), a multifunctional organelle, plays a central role in cellular signaling, development, and stress response. Dysregulation of ER homeostasis has been associated with human diseases, such as cancer, inflammation, and diabetes. A broad spectrum of stressful stimuli including hypoxia as well as a variety of pharmacological agents can lead to the ER stress response. In this study, we have developed a stable ER stress reporter cell line that stably expresses a β-lactamase reporter gene under the control of the ER stress response element (ESRE) present in the glucose-regulated protein, 78 kDa (GRP78) gene promoter. This assay has been optimized and miniaturized into a 1536-well plate format. In order to identify clinically used drugs that induce ER stress response, we screened approximately 2800 drugs from the NIH Chemical Genomics Center Pharmaceutical Collection (NPC library) using a quantitative high-throughput screening (qHTS) platform. From this study, we have identified several known ER stress inducers, such as 17-AAG (via HSP90 inhibition), as well as several novel ER stress inducers such as AMI-193 and spiperone. The confirmed drugs were further studied for their effects on the phosphorylation of eukaryotic initiation factor 2α (eIF2α), the X-box-binding protein (XBP1) splicing, and GRP78 gene expression. These results suggest that the ER stress inducers identified from the NPC library using the qHTS approach could shed new lights on the potential therapeutic targets of these drugs. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 32 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 8 | 25% |
| Student > Ph. D. Student | 5 | 16% |
| Student > Bachelor | 4 | 13% |
| Researcher | 4 | 13% |
| Student > Doctoral Student | 3 | 9% |
| Other | 5 | 16% |
| Unknown | 3 | 9% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 8 | 25% |
| Biochemistry, Genetics and Molecular Biology | 5 | 16% |
| Chemistry | 5 | 16% |
| Medicine and Dentistry | 3 | 9% |
| Nursing and Health Professions | 2 | 6% |
| Other | 4 | 13% |
| Unknown | 5 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 June 2015.
All research outputs
#20,657,128
of 25,374,917 outputs
Outputs from Analytical & Bioanalytical Chemistry
#6,601
of 9,619 outputs
Outputs of similar age
#206,211
of 278,542 outputs
Outputs of similar age from Analytical & Bioanalytical Chemistry
#68
of 183 outputs
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So far Altmetric has tracked 9,619 research outputs from this source. They receive a mean Attention Score of 3.1. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
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