Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening.

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.
Authors	Giulia Breveglieri, Salvatore Pacifico, Cristina Zuccato, Lucia Carmela Cosenza, Shaiq Sultan, Elisabetta D'Aversa, Roberto Gambari, Delia Preti, Claudio Trapella, Remo Guerrini, Monica Borgatti
Journal	International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 19 (Oct 08 2020) ISSN: 1422-0067 [Electronic] Switzerland
PMID	33050052 (Publication Type: Journal Article)
Chemical References	Luminescent Proteins Small Molecule Libraries beta-Globins enhanced green fluorescent protein gamma-Globins Green Fluorescent Proteins Fetal Hemoglobin
Topics	Anemia, Sickle Cell (blood, drug therapy) Biosensing Techniques (methods) Cell Differentiation (drug effects) Cell Proliferation (drug effects) Drug Discovery (methods) Drug Evaluation, Preclinical (methods) Fetal Hemoglobin (biosynthesis) Flow Cytometry Gene Expression (drug effects) Gene Expression Regulation (drug effects) Green Fluorescent Proteins (genetics) Humans K562 Cells Luminescent Proteins (genetics) Protein Biosynthesis (drug effects) Small Molecule Libraries (pharmacology, therapeutic use) beta-Globins (genetics) beta-Thalassemia (blood, drug therapy) gamma-Globins (genetics) Red Fluorescent Protein

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