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The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation

BACKGROUND: In the European Union, medicines are authorised for some rare disease only if they are judged to be dissimilar to authorised orphan drugs for that disease. This paper describes the use of 2D fingerprints to show the extent of the relationship between computed levels of structural similar...

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Autores principales: Franco, Pedro, Porta, Nuria, Holliday, John D, Willett, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923256/
https://www.ncbi.nlm.nih.gov/pubmed/24485002
http://dx.doi.org/10.1186/1758-2946-6-5
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author Franco, Pedro
Porta, Nuria
Holliday, John D
Willett, Peter
author_facet Franco, Pedro
Porta, Nuria
Holliday, John D
Willett, Peter
author_sort Franco, Pedro
collection PubMed
description BACKGROUND: In the European Union, medicines are authorised for some rare disease only if they are judged to be dissimilar to authorised orphan drugs for that disease. This paper describes the use of 2D fingerprints to show the extent of the relationship between computed levels of structural similarity for pairs of molecules and expert judgments of the similarities of those pairs. The resulting relationship can be used to provide input to the assessment of new active compounds for which orphan drug authorisation is being sought. RESULTS: 143 experts provided judgments of the similarity or dissimilarity of 100 pairs of drug-like molecules from the DrugBank 3.0 database. The similarities of these pairs were also computed using BCI, Daylight, ECFC4, ECFP4, MDL and Unity 2D fingerprints. Logistic regression analyses demonstrated a strong relationship between the human and computed similarity assessments, with the resulting regression models having significant predictive power in experiments using data from submissions of orphan drug medicines to the European Medicines Agency. The BCI fingerprints performed best overall on the DrugBank dataset while the BCI, Daylight, ECFP4 and Unity fingerprints performed comparably on the European Medicines Agency dataset. CONCLUSIONS: Measures of structural similarity based on 2D fingerprints can provide a useful source of information for the assessment of orphan drug status by regulatory authorities.
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spelling pubmed-39232562014-03-04 The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation Franco, Pedro Porta, Nuria Holliday, John D Willett, Peter J Cheminform Research Article BACKGROUND: In the European Union, medicines are authorised for some rare disease only if they are judged to be dissimilar to authorised orphan drugs for that disease. This paper describes the use of 2D fingerprints to show the extent of the relationship between computed levels of structural similarity for pairs of molecules and expert judgments of the similarities of those pairs. The resulting relationship can be used to provide input to the assessment of new active compounds for which orphan drug authorisation is being sought. RESULTS: 143 experts provided judgments of the similarity or dissimilarity of 100 pairs of drug-like molecules from the DrugBank 3.0 database. The similarities of these pairs were also computed using BCI, Daylight, ECFC4, ECFP4, MDL and Unity 2D fingerprints. Logistic regression analyses demonstrated a strong relationship between the human and computed similarity assessments, with the resulting regression models having significant predictive power in experiments using data from submissions of orphan drug medicines to the European Medicines Agency. The BCI fingerprints performed best overall on the DrugBank dataset while the BCI, Daylight, ECFP4 and Unity fingerprints performed comparably on the European Medicines Agency dataset. CONCLUSIONS: Measures of structural similarity based on 2D fingerprints can provide a useful source of information for the assessment of orphan drug status by regulatory authorities. BioMed Central 2014-02-01 /pmc/articles/PMC3923256/ /pubmed/24485002 http://dx.doi.org/10.1186/1758-2946-6-5 Text en Copyright © 2014 Franco et al.; licensee Chemistry Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Franco, Pedro
Porta, Nuria
Holliday, John D
Willett, Peter
The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation
title The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation
title_full The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation
title_fullStr The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation
title_full_unstemmed The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation
title_short The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation
title_sort use of 2d fingerprint methods to support the assessment of structural similarity in orphan drug legislation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923256/
https://www.ncbi.nlm.nih.gov/pubmed/24485002
http://dx.doi.org/10.1186/1758-2946-6-5
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