MS-275 Chemical Analogues Promote Hemoglobin Production and Erythroid Differentiation of K562 Cells
Ημερομηνία
2019Συγγραφέας
Voskou, StellaPhylactides, Marios
Afantitis, Andreas
Melagraki, Georgia
Tsoumanis, Andreas
Koutentis, Panayotis A.
Mitsidi, Tina
Mirallai, Styliana I.
Kleanthous, Marina
ISSN
0363-0269Source
HemoglobinVolume
43Issue
2Pages
116-121Google Scholar check
Metadata
Εμφάνιση πλήρους εγγραφήςΕπιτομή
β-Thalassemia (β-thal) is a hemoglobinopathy characterized by reduced or absent β-globin production. Pharmacological reactivation of the γ-globin gene for the production of fetal hemoglobin (Hb F) presents an attractive treatment strategy. In an effort to identify promising therapeutic agents, we evaluated 80 analogues of the histone deacetylase inhibitor MS-275, a known Hb F inducer. The chemical analogues were identified via molecular modeling and targeted chemical modifications. Nine novel agents exhibited significant hemoglobin (Hb)-inducing and erythroid differentiation activities in the human K562 erythroleukemia cell line. Five of them appeared to be stronger inducers than the lead compound, MS-275, demonstrating the effectiveness of our method.