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 ?-thalassemia and sickle cell disease. In particular, pharmacologically mediated stimulation of human ?-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 ?-globin and ?-globin gene promoters, respectively. Then the identified compounds were analyzed as HbF inducers on primary cell cultures, obtained from ?-thalassemia patients, confirming their activity as HbF inducers, and suggesting these molecules as lead compounds for further chemical and biological investigations.

SUBMITTER: Breveglieri G 

PROVIDER: S-EPMC7582302 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature