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Large-scale detection of drug off-targets: hypotheses for drug repurposing and understanding side-effects

Overview of attention for article published in BMC Pharmacology and Toxicology, April 2017
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (74th percentile)

Mentioned by

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11 tweeters

Citations

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26 Dimensions

Readers on

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75 Mendeley
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Title
Large-scale detection of drug off-targets: hypotheses for drug repurposing and understanding side-effects
Published in
BMC Pharmacology and Toxicology, April 2017
DOI 10.1186/s40360-017-0128-7
Pubmed ID
Authors

Matthieu Chartier, Louis-Philippe Morency, María Inés Zylber, Rafael J. Najmanovich

Abstract

Promiscuity in molecular interactions between small-molecules, including drugs, and proteins is widespread. Such unintended interactions can be exploited to suggest drug repurposing possibilities as well as to identify potential molecular mechanisms responsible for observed side-effects. We perform a large-scale analysis to detect binding-site molecular interaction field similarities between the binding-sites of the primary target of 400 drugs against a dataset of 14082 cavities within 7895 different proteins representing a non-redundant dataset of all proteins with known structure. Statistically-significant cases with high levels of similarities represent potential cases where the drugs that bind the original target may in principle bind the suggested off-target. Such cases are further analysed with docking simulations to verify if indeed the drug could, in principle, bind the off-target. Diverse sources of data are integrated to associated potential cross-reactivity targets with side-effects. We observe that promiscuous binding-sites tend to display higher levels of hydrophobic and aromatic similarities. Focusing on the most statistically significant similarities (Z-score ≥ 3.0) and corroborating docking results (RMSD < 2.0 Å), we find 2923 cases involving 140 unique drugs and 1216 unique potential cross-reactivity protein targets. We highlight a few cases with a potential for drug repurposing (acetazolamide as a chorismate pyruvate lyase inhibitor, raloxifene as a bacterial quorum sensing inhibitor) as well as to explain the side-effects of zanamivir and captopril. A web-interface permits to explore the detected similarities for each of the 400 binding-sites of the primary drug targets and visualise them for the most statistically significant cases. The detection of molecular interaction field similarities provide the opportunity to suggest drug repurposing opportunities as well as to identify potential molecular mechanisms responsible for side-effects. All methods utilized are freely available and can be readily applied to new query binding-sites. All data is freely available and represents an invaluable source to identify further candidates for repurposing and suggest potential mechanisms responsible for side-effects.

Twitter Demographics

The data shown below were collected from the profiles of 11 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 75 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 1%
Unknown 74 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 23%
Researcher 14 19%
Student > Bachelor 12 16%
Student > Master 8 11%
Professor > Associate Professor 4 5%
Other 11 15%
Unknown 9 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 22 29%
Agricultural and Biological Sciences 16 21%
Chemistry 5 7%
Pharmacology, Toxicology and Pharmaceutical Science 5 7%
Medicine and Dentistry 5 7%
Other 7 9%
Unknown 15 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 07 July 2020.
All research outputs
#3,764,246
of 19,146,896 outputs
Outputs from BMC Pharmacology and Toxicology
#72
of 374 outputs
Outputs of similar age
#71,515
of 277,283 outputs
Outputs of similar age from BMC Pharmacology and Toxicology
#2
of 2 outputs
Altmetric has tracked 19,146,896 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 374 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one has done well, scoring higher than 81% of its peers.
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 277,283 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 74% of its contemporaries.
We're also able to compare this research output to 2 others from the same source and published within six weeks on either side of this one.