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Mendeley readers
Attention Score in Context
| Title |
Discovery and validation of small-molecule heat-shock protein 90 inhibitors through multimodality molecular imaging in living subjects
|
|---|---|
| Published in |
Proceedings of the National Academy of Sciences of the United States of America, August 2012
|
| DOI | 10.1073/pnas.1205459109 |
| Pubmed ID | |
| Authors |
Carmel T. Chan, Robert E. Reeves, Ron Geller, Shahriar S. Yaghoubi, Aileen Hoehne, David E. Solow-Cordero, Gabriela Chiosis, Tarik F. Massoud, Ramasamy Paulmurugan, Sanjiv S. Gambhir |
| Abstract |
Up-regulation of the folding machinery of the heat-shock protein 90 (Hsp90) chaperone protein is crucial for cancer progression. The two Hsp90 isoforms (α and β) play different roles in response to chemotherapy. To identify isoform-selective inhibitors of Hsp90(α/β)/cochaperone p23 interactions, we developed a dual-luciferase (Renilla and Firefly) reporter system for high-throughput screening (HTS) and monitoring the efficacy of Hsp90 inhibitors in cell culture and live mice. HTS of a 30,176 small-molecule chemical library in cell culture identified a compound, N-(5-methylisoxazol-3-yl)-2-[4-(thiophen-2-yl)-6-(trifluoromethyl)pyrimidin-2-ylthio]acetamide (CP9), that binds to Hsp90(α/β) and displays characteristics of Hsp90 inhibitors, i.e., degradation of Hsp90 client proteins and inhibition of cell proliferation, glucose metabolism, and thymidine kinase activity, in multiple cancer cell lines. The efficacy of CP9 in disrupting Hsp90(α/β)/p23 interactions and cell proliferation in tumor xenografts was evaluated by non-invasive, repetitive Renilla luciferase and Firefly luciferase imaging, respectively. At 38 h posttreatment (80 mg/kg × 3, i.p.), CP9 led to selective disruption of Hsp90α/p23 as compared with Hsp90β/p23 interactions. Small-animal PET/CT in the same cohort of mice showed that CP9 treatment (43 h) led to a 40% decrease in (18)F-fluorodeoxyglucose uptake in tumors relative to carrier control-treated mice. However, CP9 did not lead to significant degradation of Hsp90 client proteins in tumors. We performed a structural activity relationship study with 62 analogs of CP9 and identified A17 as the lead compound that outperformed CP9 in inhibiting Hsp90(α/β)/p23 interactions in cell culture. Our efforts demonstrated the power of coupling of HTS with multimodality molecular imaging and led to identification of Hsp90 inhibitors. |
Mendeley readers
The data shown below were compiled from readership statistics for 46 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 2% |
| Romania | 1 | 2% |
| Switzerland | 1 | 2% |
| Austria | 1 | 2% |
| Unknown | 42 | 91% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 12 | 26% |
| Student > Ph. D. Student | 9 | 20% |
| Professor > Associate Professor | 6 | 13% |
| Student > Master | 6 | 13% |
| Student > Postgraduate | 3 | 7% |
| Other | 6 | 13% |
| Unknown | 4 | 9% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 10 | 22% |
| Medicine and Dentistry | 8 | 17% |
| Chemistry | 7 | 15% |
| Biochemistry, Genetics and Molecular Biology | 6 | 13% |
| Engineering | 3 | 7% |
| Other | 4 | 9% |
| Unknown | 8 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 15 April 2014.
All research outputs
#8,219,054
of 24,625,114 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#64,491
of 101,438 outputs
Outputs of similar age
#58,284
of 173,460 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#635
of 923 outputs
Altmetric has tracked 24,625,114 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 101,438 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 38.8. This one is in the 15th percentile – i.e., 15% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 173,460 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 923 others from the same source and published within six weeks on either side of this one. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.