A novel approach in glioblastoma multiforme drug discovery: perturbation studies in vitro
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/107083 https://doi.org/10.7324/JAPS.2019.90407 |
Resumo: | Despite impressive advances in drug discovery methods, predicting cellular response to anticancer drugs remains challenging. In glioblastoma multiforme, this fact is even marked as many promising drugs were followed by disappointment. As a result, the aim of this study is to clarify the effects of inhibition of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in glioblastoma multiforme, while exploring how the focus on potency might ignore the potential impact of variation in other pharmacological parameters. The evaluation of the induced drug perturbation in glioblastoma cancer cells and a multiparametric characterization dose-response of two PDK1 inhibitors were performed. Singular analysis of potency would lead to the conclusion that FC100 compound would be the most promising to treat glioblastoma multiforme. However, exploring other pharmacological parameters shows the opposite giving more information about the cell response. The study shows that potency should not be the critical factor in developing new drugs as our most potent compound lacks growth inhibition effect. So, the evaluation of promising drugs during the drug discovery phase needs to be re-evaluated and multiparametric dose-response analysis might be a useful approach to compare drugs and potentially better characterization of both drug and disease profiles. |
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A novel approach in glioblastoma multiforme drug discovery: perturbation studies in vitroDrug discovery & developmentquantitative & systems pharmacologyperturbation studiesmultiparametric doseresponse analysesglioblastoma multiformePDK1 inhibitorsDespite impressive advances in drug discovery methods, predicting cellular response to anticancer drugs remains challenging. In glioblastoma multiforme, this fact is even marked as many promising drugs were followed by disappointment. As a result, the aim of this study is to clarify the effects of inhibition of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in glioblastoma multiforme, while exploring how the focus on potency might ignore the potential impact of variation in other pharmacological parameters. The evaluation of the induced drug perturbation in glioblastoma cancer cells and a multiparametric characterization dose-response of two PDK1 inhibitors were performed. Singular analysis of potency would lead to the conclusion that FC100 compound would be the most promising to treat glioblastoma multiforme. However, exploring other pharmacological parameters shows the opposite giving more information about the cell response. The study shows that potency should not be the critical factor in developing new drugs as our most potent compound lacks growth inhibition effect. So, the evaluation of promising drugs during the drug discovery phase needs to be re-evaluated and multiparametric dose-response analysis might be a useful approach to compare drugs and potentially better characterization of both drug and disease profiles.MediPoeia2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107083http://hdl.handle.net/10316/107083https://doi.org/10.7324/JAPS.2019.90407eng22313354Oliveira, Luís CarlosMarques, Maria PaulaCaseiro, Armando JoséRapposelli, SimonaCarvalho, Ana Lúcia Batista deFonseca, Ana Paulainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-05-11T12:01:04Zoai:estudogeral.uc.pt:10316/107083Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:27.422294Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
A novel approach in glioblastoma multiforme drug discovery: perturbation studies in vitro |
title |
A novel approach in glioblastoma multiforme drug discovery: perturbation studies in vitro |
spellingShingle |
A novel approach in glioblastoma multiforme drug discovery: perturbation studies in vitro Oliveira, Luís Carlos Drug discovery & development quantitative & systems pharmacology perturbation studies multiparametric doseresponse analyses glioblastoma multiforme PDK1 inhibitors |
title_short |
A novel approach in glioblastoma multiforme drug discovery: perturbation studies in vitro |
title_full |
A novel approach in glioblastoma multiforme drug discovery: perturbation studies in vitro |
title_fullStr |
A novel approach in glioblastoma multiforme drug discovery: perturbation studies in vitro |
title_full_unstemmed |
A novel approach in glioblastoma multiforme drug discovery: perturbation studies in vitro |
title_sort |
A novel approach in glioblastoma multiforme drug discovery: perturbation studies in vitro |
author |
Oliveira, Luís Carlos |
author_facet |
Oliveira, Luís Carlos Marques, Maria Paula Caseiro, Armando José Rapposelli, Simona Carvalho, Ana Lúcia Batista de Fonseca, Ana Paula |
author_role |
author |
author2 |
Marques, Maria Paula Caseiro, Armando José Rapposelli, Simona Carvalho, Ana Lúcia Batista de Fonseca, Ana Paula |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Oliveira, Luís Carlos Marques, Maria Paula Caseiro, Armando José Rapposelli, Simona Carvalho, Ana Lúcia Batista de Fonseca, Ana Paula |
dc.subject.por.fl_str_mv |
Drug discovery & development quantitative & systems pharmacology perturbation studies multiparametric doseresponse analyses glioblastoma multiforme PDK1 inhibitors |
topic |
Drug discovery & development quantitative & systems pharmacology perturbation studies multiparametric doseresponse analyses glioblastoma multiforme PDK1 inhibitors |
description |
Despite impressive advances in drug discovery methods, predicting cellular response to anticancer drugs remains challenging. In glioblastoma multiforme, this fact is even marked as many promising drugs were followed by disappointment. As a result, the aim of this study is to clarify the effects of inhibition of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in glioblastoma multiforme, while exploring how the focus on potency might ignore the potential impact of variation in other pharmacological parameters. The evaluation of the induced drug perturbation in glioblastoma cancer cells and a multiparametric characterization dose-response of two PDK1 inhibitors were performed. Singular analysis of potency would lead to the conclusion that FC100 compound would be the most promising to treat glioblastoma multiforme. However, exploring other pharmacological parameters shows the opposite giving more information about the cell response. The study shows that potency should not be the critical factor in developing new drugs as our most potent compound lacks growth inhibition effect. So, the evaluation of promising drugs during the drug discovery phase needs to be re-evaluated and multiparametric dose-response analysis might be a useful approach to compare drugs and potentially better characterization of both drug and disease profiles. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/107083 http://hdl.handle.net/10316/107083 https://doi.org/10.7324/JAPS.2019.90407 |
url |
http://hdl.handle.net/10316/107083 https://doi.org/10.7324/JAPS.2019.90407 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
22313354 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MediPoeia |
publisher.none.fl_str_mv |
MediPoeia |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134121538093056 |