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.

Discovery of novel fetal hemoglobin inducers for β-thalassemia by small chemical library screening

Breveglieri G
Primo
;
Salvatore Pacifico
Secondo
;
Cristina Zuccato;Lucia Carmela Cosenza;Shaiq Sultan;Elisabetta D’Aversa;Roberto Gambari;Delia Preti;Claudio Trapella;Remo Guerrini
Penultimo
;
Monica Borgatti
Ultimo
2020

Abstract

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.
Breveglieri, G; Pacifico, Salvatore; Zuccato, Cristina; Cosenza, Lucia Carmela; Sultan, Shaiq; D'Aversa, Elisabetta; Gambari, Roberto; Preti, Delia; Trapella, Claudio; Guerrini, Remo; Borgatti, Monica
File in questo prodotto:
File Dimensione Formato  
Discovery of novel fetal hemoglobin inducers for β-thalassemia by small chemical library screening - MDPI - ottobre 2020.pdf

accesso aperto

Descrizione: Full text editoriale
Tipologia: Full text (versione editoriale)
Licenza: Creative commons
Dimensione 2.92 MB
Formato Adobe PDF
2.92 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2426252
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 1
social impact