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Mendeley readers
Attention Score in Context
| Title |
A Novel Flow Cytometric HTS Assay Reveals Functional Modulators of ATP Binding Cassette Transporter ABCB6
|
|---|---|
| Published in |
PLOS ONE, July 2012
|
| DOI | 10.1371/journal.pone.0040005 |
| Pubmed ID | |
| Authors |
Kishore Polireddy, Mohiuddin Md. Taimur Khan, Hemantkumar Chavan, Susan Young, Xiaochao Ma, Anna Waller, Matthew Garcia, Dominique Perez, Stephanie Chavez, Jacob J. Strouse, Mark K. Haynes, Cristian G. Bologa, Tudor I. Oprea, George P. Tegos, Larry A. Sklar, Partha Krishnamurthy |
| Abstract |
ABCB6 is a member of the adenosine triphosphate (ATP)-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS), can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity. |
Mendeley readers
The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 2% |
| Unknown | 50 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 12 | 24% |
| Researcher | 8 | 16% |
| Student > Master | 7 | 14% |
| Student > Doctoral Student | 6 | 12% |
| Other | 4 | 8% |
| Other | 11 | 22% |
| Unknown | 3 | 6% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 19 | 37% |
| Medicine and Dentistry | 6 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 10% |
| Biochemistry, Genetics and Molecular Biology | 5 | 10% |
| Chemistry | 4 | 8% |
| Other | 7 | 14% |
| Unknown | 5 | 10% |
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 16 July 2012.
All research outputs
#20,161,674
of 22,671,366 outputs
Outputs from PLOS ONE
#172,677
of 193,517 outputs
Outputs of similar age
#147,943
of 164,332 outputs
Outputs of similar age from PLOS ONE
#3,616
of 3,945 outputs
Altmetric has tracked 22,671,366 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 193,517 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 1st percentile – i.e., 1% 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 164,332 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3,945 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.