Pharmacological induction of the fetal γ globin gene and the consequent formation of HbF (α2/γ2) in adult erythroid cells is one feasible therapeutic strategy for sickle cell disease (SCD) and severe β-thalassemias. Hydroxyurea (HU) is the current drug of choice for SCD, but the serious side effects limit its clinical use. Moreover, 30-50% of patients are irresponsive to HU treatment. We have identified several potent γ globin-inducers. Remarkably, our compound induces the γ globin gene in HU-resistant primary human adult erythroid cells. This study provides a new framework for the development of new and superior compounds for treating SCD and the severe β-thalassemias.