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Drug Repurposing by Simulating Flow Through Protein–Protein Interaction Networks

As drug development is extremely expensive, the identification of novel indications for in‐market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining simulation of intracellular networks and machine learning are curren...

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Autores principales: Manczinger, M, Bodnár, VÁ, Papp, BT, Bolla, SB, Szabó, K, Balázs, B, Csányi, E, Szél, E, Erős, G, Kemény, L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836852/
https://www.ncbi.nlm.nih.gov/pubmed/28643328
http://dx.doi.org/10.1002/cpt.769
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author Manczinger, M
Bodnár, VÁ
Papp, BT
Bolla, SB
Szabó, K
Balázs, B
Csányi, E
Szél, E
Erős, G
Kemény, L
author_facet Manczinger, M
Bodnár, VÁ
Papp, BT
Bolla, SB
Szabó, K
Balázs, B
Csányi, E
Szél, E
Erős, G
Kemény, L
author_sort Manczinger, M
collection PubMed
description As drug development is extremely expensive, the identification of novel indications for in‐market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining simulation of intracellular networks and machine learning are currently not available. We developed an algorithm that simulates drug effects on the flow of information through protein–protein interaction networks, and used support vector machine to identify potentially effective drugs in our model disease, psoriasis. Using this method, we screened about 1,500 marketed and investigational substances, identified 51 drugs that were potentially effective, and selected three of them for experimental confirmation. All drugs inhibited tumor necrosis factor alpha‐induced nuclear factor kappa B activity in vitro, suggesting they might be effective for treating psoriasis in humans. Additionally, these drugs significantly inhibited imiquimod‐induced ear thickening and inflammation in the mouse model of the disease. All results suggest high prediction performance for the algorithm.
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spelling pubmed-58368522018-03-07 Drug Repurposing by Simulating Flow Through Protein–Protein Interaction Networks Manczinger, M Bodnár, VÁ Papp, BT Bolla, SB Szabó, K Balázs, B Csányi, E Szél, E Erős, G Kemény, L Clin Pharmacol Ther Research As drug development is extremely expensive, the identification of novel indications for in‐market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining simulation of intracellular networks and machine learning are currently not available. We developed an algorithm that simulates drug effects on the flow of information through protein–protein interaction networks, and used support vector machine to identify potentially effective drugs in our model disease, psoriasis. Using this method, we screened about 1,500 marketed and investigational substances, identified 51 drugs that were potentially effective, and selected three of them for experimental confirmation. All drugs inhibited tumor necrosis factor alpha‐induced nuclear factor kappa B activity in vitro, suggesting they might be effective for treating psoriasis in humans. Additionally, these drugs significantly inhibited imiquimod‐induced ear thickening and inflammation in the mouse model of the disease. All results suggest high prediction performance for the algorithm. John Wiley and Sons Inc. 2017-07-29 2018-03 /pmc/articles/PMC5836852/ /pubmed/28643328 http://dx.doi.org/10.1002/cpt.769 Text en © 2017 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research
Manczinger, M
Bodnár, VÁ
Papp, BT
Bolla, SB
Szabó, K
Balázs, B
Csányi, E
Szél, E
Erős, G
Kemény, L
Drug Repurposing by Simulating Flow Through Protein–Protein Interaction Networks
title Drug Repurposing by Simulating Flow Through Protein–Protein Interaction Networks
title_full Drug Repurposing by Simulating Flow Through Protein–Protein Interaction Networks
title_fullStr Drug Repurposing by Simulating Flow Through Protein–Protein Interaction Networks
title_full_unstemmed Drug Repurposing by Simulating Flow Through Protein–Protein Interaction Networks
title_short Drug Repurposing by Simulating Flow Through Protein–Protein Interaction Networks
title_sort drug repurposing by simulating flow through protein–protein interaction networks
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836852/
https://www.ncbi.nlm.nih.gov/pubmed/28643328
http://dx.doi.org/10.1002/cpt.769
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