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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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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. |
format | Online Article Text |
id | pubmed-3923256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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