Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors

Autores
Comelli, Nieves Carolina; Ortiz, Erlinda del Valle; Kolacz, Magdalena; Toropova, Alla P.; Toropov, Andrey A.; Duchowicz, Pablo Román; Castro, Eduardo Alberto
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The main idea of this work was to find predictive quantitative structure–activity relationships (QSAR) for a wide set of c-Src tyrosine kinase inhibitors, by means of resorting to a conformation-independent representation of the chemical structure. In this way, our attempt was to avoid the availability of X-ray crystallographic structural information of the target. Therefore, in a set composed of 80 pyrrolo-pyrimidine derivatives, 1179 theoretical descriptors were simultaneously analyzed through linear regression models obtained with the replacement method variable subset selection technique. Alternatively, the flexible (activity dependent) descriptor approach was also applied in this study. The models were validated and tested through the use of an external test set of compounds, the leave-group-out cross validation method, Y-randomization and applicability domain analysis. Our results were compared with previously published ones based on docking analysis and 3D-QSAR. The obtained conformation-independent approach was in good agreement with experimental observations.
Fil: Comelli, Nieves Carolina. Universidad Nacional de Catamarca. Facultad de Ciencias Agrarias; Argentina
Fil: Ortiz, Erlinda del Valle. Universidad Nacional de Catamarca. Facultad de Tecnologia y Ciencias Aplicadas; Argentina
Fil: Kolacz, Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Toropova, Alla P.. Istituto di Ricerche Farmacologiche Mario Negri; Italia
Fil: Toropov, Andrey A.. Istituto di Ricerche Farmacologiche Mario Negri; Italia
Fil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Castro, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Materia
Qsar Theory
Multivariable Linear Regression Analysis
C-Src Tyrosine Kinase
Structural Descriptors
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/5268
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/5268
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Conformation-Independent QSAR on c-Src Tyrosine Kinase InhibitorsComelli, Nieves CarolinaOrtiz, Erlinda del ValleKolacz, MagdalenaToropova, Alla P.Toropov, Andrey A.Duchowicz, Pablo RománCastro, Eduardo AlbertoQsar TheoryMultivariable Linear Regression AnalysisC-Src Tyrosine KinaseStructural Descriptorshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The main idea of this work was to find predictive quantitative structure–activity relationships (QSAR) for a wide set of c-Src tyrosine kinase inhibitors, by means of resorting to a conformation-independent representation of the chemical structure. In this way, our attempt was to avoid the availability of X-ray crystallographic structural information of the target. Therefore, in a set composed of 80 pyrrolo-pyrimidine derivatives, 1179 theoretical descriptors were simultaneously analyzed through linear regression models obtained with the replacement method variable subset selection technique. Alternatively, the flexible (activity dependent) descriptor approach was also applied in this study. The models were validated and tested through the use of an external test set of compounds, the leave-group-out cross validation method, Y-randomization and applicability domain analysis. Our results were compared with previously published ones based on docking analysis and 3D-QSAR. The obtained conformation-independent approach was in good agreement with experimental observations.Fil: Comelli, Nieves Carolina. Universidad Nacional de Catamarca. Facultad de Ciencias Agrarias; ArgentinaFil: Ortiz, Erlinda del Valle. Universidad Nacional de Catamarca. Facultad de Tecnologia y Ciencias Aplicadas; ArgentinaFil: Kolacz, Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Toropova, Alla P.. Istituto di Ricerche Farmacologiche Mario Negri; ItaliaFil: Toropov, Andrey A.. Istituto di Ricerche Farmacologiche Mario Negri; ItaliaFil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Castro, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaElsevier2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/5268Comelli, Nieves Carolina; Ortiz, Erlinda del Valle; Kolacz, Magdalena; Toropova, Alla P.; Toropov, Andrey A.; et al.; Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors; Elsevier; Chemometrics and Intelligent Laboratory Systems; 134; 3-2014; 47-520169-7439enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0169743914000446info:eu-repo/semantics/altIdentifier/url/10.1016/j.chemolab.2014.03.003info:eu-repo/semantics/altIdentifier/doi/10.1016/j.chemolab.2014.03.003info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:11Zoai:ri.conicet.gov.ar:11336/5268instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:58:11.646CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors
title Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors
spellingShingle Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors
Comelli, Nieves Carolina
Qsar Theory
Multivariable Linear Regression Analysis
C-Src Tyrosine Kinase
Structural Descriptors
title_short Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors
title_full Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors
title_fullStr Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors
title_full_unstemmed Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors
title_sort Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors
dc.creator.none.fl_str_mv Comelli, Nieves Carolina
Ortiz, Erlinda del Valle
Kolacz, Magdalena
Toropova, Alla P.
Toropov, Andrey A.
Duchowicz, Pablo Román
Castro, Eduardo Alberto
author Comelli, Nieves Carolina
author_facet Comelli, Nieves Carolina
Ortiz, Erlinda del Valle
Kolacz, Magdalena
Toropova, Alla P.
Toropov, Andrey A.
Duchowicz, Pablo Román
Castro, Eduardo Alberto
author_role author
author2 Ortiz, Erlinda del Valle
Kolacz, Magdalena
Toropova, Alla P.
Toropov, Andrey A.
Duchowicz, Pablo Román
Castro, Eduardo Alberto
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Qsar Theory
Multivariable Linear Regression Analysis
C-Src Tyrosine Kinase
Structural Descriptors
topic Qsar Theory
Multivariable Linear Regression Analysis
C-Src Tyrosine Kinase
Structural Descriptors
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The main idea of this work was to find predictive quantitative structure–activity relationships (QSAR) for a wide set of c-Src tyrosine kinase inhibitors, by means of resorting to a conformation-independent representation of the chemical structure. In this way, our attempt was to avoid the availability of X-ray crystallographic structural information of the target. Therefore, in a set composed of 80 pyrrolo-pyrimidine derivatives, 1179 theoretical descriptors were simultaneously analyzed through linear regression models obtained with the replacement method variable subset selection technique. Alternatively, the flexible (activity dependent) descriptor approach was also applied in this study. The models were validated and tested through the use of an external test set of compounds, the leave-group-out cross validation method, Y-randomization and applicability domain analysis. Our results were compared with previously published ones based on docking analysis and 3D-QSAR. The obtained conformation-independent approach was in good agreement with experimental observations.
Fil: Comelli, Nieves Carolina. Universidad Nacional de Catamarca. Facultad de Ciencias Agrarias; Argentina
Fil: Ortiz, Erlinda del Valle. Universidad Nacional de Catamarca. Facultad de Tecnologia y Ciencias Aplicadas; Argentina
Fil: Kolacz, Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Toropova, Alla P.. Istituto di Ricerche Farmacologiche Mario Negri; Italia
Fil: Toropov, Andrey A.. Istituto di Ricerche Farmacologiche Mario Negri; Italia
Fil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Castro, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
description The main idea of this work was to find predictive quantitative structure–activity relationships (QSAR) for a wide set of c-Src tyrosine kinase inhibitors, by means of resorting to a conformation-independent representation of the chemical structure. In this way, our attempt was to avoid the availability of X-ray crystallographic structural information of the target. Therefore, in a set composed of 80 pyrrolo-pyrimidine derivatives, 1179 theoretical descriptors were simultaneously analyzed through linear regression models obtained with the replacement method variable subset selection technique. Alternatively, the flexible (activity dependent) descriptor approach was also applied in this study. The models were validated and tested through the use of an external test set of compounds, the leave-group-out cross validation method, Y-randomization and applicability domain analysis. Our results were compared with previously published ones based on docking analysis and 3D-QSAR. The obtained conformation-independent approach was in good agreement with experimental observations.
publishDate 2014
dc.date.none.fl_str_mv 2014-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/5268
Comelli, Nieves Carolina; Ortiz, Erlinda del Valle; Kolacz, Magdalena; Toropova, Alla P.; Toropov, Andrey A.; et al.; Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors; Elsevier; Chemometrics and Intelligent Laboratory Systems; 134; 3-2014; 47-52
0169-7439
url http://hdl.handle.net/11336/5268
identifier_str_mv Comelli, Nieves Carolina; Ortiz, Erlinda del Valle; Kolacz, Magdalena; Toropova, Alla P.; Toropov, Andrey A.; et al.; Conformation-Independent QSAR on c-Src Tyrosine Kinase Inhibitors; Elsevier; Chemometrics and Intelligent Laboratory Systems; 134; 3-2014; 47-52
0169-7439
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0169743914000446
info:eu-repo/semantics/altIdentifier/url/10.1016/j.chemolab.2014.03.003
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.chemolab.2014.03.003
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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