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Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening
The screening of chemical libraries based on cellular biosensors is a useful approach to identify new hits for novel therapeutic targets involved in rare genetic pathologies, such as β-thalassemia and sickle cell disease. In particular, pharmacologically mediated stimulation of human γ-globin gene e...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582302/ https://www.ncbi.nlm.nih.gov/pubmed/33050052 http://dx.doi.org/10.3390/ijms21197426 |
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author | Breveglieri, Giulia Pacifico, Salvatore Zuccato, Cristina Cosenza, Lucia Carmela Sultan, Shaiq D’Aversa, Elisabetta Gambari, Roberto Preti, Delia Trapella, Claudio Guerrini, Remo Borgatti, Monica |
author_facet | Breveglieri, Giulia Pacifico, Salvatore Zuccato, Cristina Cosenza, Lucia Carmela Sultan, Shaiq D’Aversa, Elisabetta Gambari, Roberto Preti, Delia Trapella, Claudio Guerrini, Remo Borgatti, Monica |
author_sort | Breveglieri, Giulia |
collection | PubMed |
description | The screening of chemical libraries based on cellular biosensors is a useful approach to identify new hits for novel therapeutic targets involved in rare genetic pathologies, such as β-thalassemia and sickle cell disease. In particular, pharmacologically mediated stimulation of human γ-globin gene expression, and increase of fetal hemoglobin (HbF) production, have been suggested as potential therapeutic strategies for these hemoglobinopathies. In this article, we screened a small chemical library, constituted of 150 compounds, using the cellular biosensor K562.GR, carrying enhanced green fluorescence protein (EGFP) and red fluorescence protein (RFP) genes under the control of the human γ-globin and β-globin gene promoters, respectively. Then the identified compounds were analyzed as HbF inducers on primary cell cultures, obtained from β-thalassemia patients, confirming their activity as HbF inducers, and suggesting these molecules as lead compounds for further chemical and biological investigations. |
format | Online Article Text |
id | pubmed-7582302 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75823022020-10-28 Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening Breveglieri, Giulia Pacifico, Salvatore Zuccato, Cristina Cosenza, Lucia Carmela Sultan, Shaiq D’Aversa, Elisabetta Gambari, Roberto Preti, Delia Trapella, Claudio Guerrini, Remo Borgatti, Monica Int J Mol Sci Article The screening of chemical libraries based on cellular biosensors is a useful approach to identify new hits for novel therapeutic targets involved in rare genetic pathologies, such as β-thalassemia and sickle cell disease. In particular, pharmacologically mediated stimulation of human γ-globin gene expression, and increase of fetal hemoglobin (HbF) production, have been suggested as potential therapeutic strategies for these hemoglobinopathies. In this article, we screened a small chemical library, constituted of 150 compounds, using the cellular biosensor K562.GR, carrying enhanced green fluorescence protein (EGFP) and red fluorescence protein (RFP) genes under the control of the human γ-globin and β-globin gene promoters, respectively. Then the identified compounds were analyzed as HbF inducers on primary cell cultures, obtained from β-thalassemia patients, confirming their activity as HbF inducers, and suggesting these molecules as lead compounds for further chemical and biological investigations. MDPI 2020-10-08 /pmc/articles/PMC7582302/ /pubmed/33050052 http://dx.doi.org/10.3390/ijms21197426 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Breveglieri, Giulia Pacifico, Salvatore Zuccato, Cristina Cosenza, Lucia Carmela Sultan, Shaiq D’Aversa, Elisabetta Gambari, Roberto Preti, Delia Trapella, Claudio Guerrini, Remo Borgatti, Monica Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening |
title | Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening |
title_full | Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening |
title_fullStr | Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening |
title_full_unstemmed | Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening |
title_short | Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening |
title_sort | discovery of novel fetal hemoglobin inducers through small chemical library screening |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582302/ https://www.ncbi.nlm.nih.gov/pubmed/33050052 http://dx.doi.org/10.3390/ijms21197426 |
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