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Promiscuity progression of bioactive compounds over time

In the context of polypharmacology, compound promiscuity is rationalized as the ability of small molecules to specifically interact with multiple targets. To study promiscuity progression of bioactive compounds in detail, nearly 1 million compounds and more than 5.2 million activity records were ana...

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Autores principales: Hu, Ye, Jasial, Swarit, Bajorath, Jürgen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000Research 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448747/
https://www.ncbi.nlm.nih.gov/pubmed/26064479
http://dx.doi.org/10.12688/f1000research.6473.1
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author Hu, Ye
Jasial, Swarit
Bajorath, Jürgen
author_facet Hu, Ye
Jasial, Swarit
Bajorath, Jürgen
author_sort Hu, Ye
collection PubMed
description In the context of polypharmacology, compound promiscuity is rationalized as the ability of small molecules to specifically interact with multiple targets. To study promiscuity progression of bioactive compounds in detail, nearly 1 million compounds and more than 5.2 million activity records were analyzed. Compound sets were assembled by applying different data confidence criteria and selecting compounds with activity histories over many years. On the basis of release dates, compounds and activity records were organized on a time course, which ultimately enabled monitoring data growth and promiscuity progression over nearly 40 years, beginning in 1976. Surprisingly low degrees of promiscuity were consistently detected for all compound sets and there were only small increases in promiscuity over time. In fact, most compounds had a constant degree of promiscuity, including compounds with an activity history of 10 or 20 years. Moreover, during periods of massive data growth, beginning in 2007, promiscuity degrees also remained constant or displayed only minor increases, depending on the activity data confidence levels. Considering high-confidence data, bioactive compounds currently interact with 1.5 targets on average, regardless of their origins, and display essentially constant degrees of promiscuity over time. Taken together, our findings provide expectation values for promiscuity progression and magnitudes among bioactive compounds as activity data further grow.
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spelling pubmed-44487472015-06-09 Promiscuity progression of bioactive compounds over time Hu, Ye Jasial, Swarit Bajorath, Jürgen F1000Res Research Article In the context of polypharmacology, compound promiscuity is rationalized as the ability of small molecules to specifically interact with multiple targets. To study promiscuity progression of bioactive compounds in detail, nearly 1 million compounds and more than 5.2 million activity records were analyzed. Compound sets were assembled by applying different data confidence criteria and selecting compounds with activity histories over many years. On the basis of release dates, compounds and activity records were organized on a time course, which ultimately enabled monitoring data growth and promiscuity progression over nearly 40 years, beginning in 1976. Surprisingly low degrees of promiscuity were consistently detected for all compound sets and there were only small increases in promiscuity over time. In fact, most compounds had a constant degree of promiscuity, including compounds with an activity history of 10 or 20 years. Moreover, during periods of massive data growth, beginning in 2007, promiscuity degrees also remained constant or displayed only minor increases, depending on the activity data confidence levels. Considering high-confidence data, bioactive compounds currently interact with 1.5 targets on average, regardless of their origins, and display essentially constant degrees of promiscuity over time. Taken together, our findings provide expectation values for promiscuity progression and magnitudes among bioactive compounds as activity data further grow. F1000Research 2015-05-13 /pmc/articles/PMC4448747/ /pubmed/26064479 http://dx.doi.org/10.12688/f1000research.6473.1 Text en Copyright: © 2015 Hu Y et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/publicdomain/zero/1.0/ Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).
spellingShingle Research Article
Hu, Ye
Jasial, Swarit
Bajorath, Jürgen
Promiscuity progression of bioactive compounds over time
title Promiscuity progression of bioactive compounds over time
title_full Promiscuity progression of bioactive compounds over time
title_fullStr Promiscuity progression of bioactive compounds over time
title_full_unstemmed Promiscuity progression of bioactive compounds over time
title_short Promiscuity progression of bioactive compounds over time
title_sort promiscuity progression of bioactive compounds over time
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448747/
https://www.ncbi.nlm.nih.gov/pubmed/26064479
http://dx.doi.org/10.12688/f1000research.6473.1
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