MS-275 Chemical Analogues Promote Hemoglobin Production and Erythroid Differentiation of K562 Cells

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.