Table 1.

Summary of drugs that induce HbF through the Keap1/NRF2 pathway.

Drug	Structure	Effect	References
Sulforaphane (SFN)		Induce HbF expression in primary erythroid progenitors; increase mRNA levels of NRF2 target HMOX1 gene in SCD patients	Doss et al.65
Dimethyl fumarate (DMF)		Induce HbF in normal and sickle erythroid progenitors; induce HbF in SCD mice; decrease inflammation factor expression in SCD mice.	Zhu et al.60 Krishnamoorthy et al.58 Belcher et al.90
Tertiary butylhydroquinone (tBHQ)		Induces NRF2 activation and binding to γ-globin promoter; Increase γ-globin expression and HbF level in K562 and primary erythroid progenitors; increased NOx levels in SCD patients	Macari et al.62 Hoppe et al.91
Simvastatin		Increase γ-globin expression and HbF level in K562 and primary erythroid progenitors by NRF2 activation and inhibits β-globin transcription by suppression KLF1 and BCL11A	Macari and Lowrey59
MLN9708		Inhibits proteasome mediated ubiquitination and degradation of NRF2; induces ROS generation and antioxidant response in B-CFU cells from SCD patient; induces NRF2 nuclear localization; Increases HbF level in K562 cells	Kupperman et al.92 Pullarkat et al.93
N-acetylcysteine (NAC)		Induce GSH biosynthesis;	Dodd et al.94
3H-1,2-dithiole-3-thione (D3T)		Induce GSH biosynthesis; modulate inflammatory response in SCD mouse	Manandhar et al.95 Ghosh et al.54

NRF2: Nuclear factor (erythroid-derived 2)-like 2; SCD: sickle cell disease; HbF: fetal hemoglobin.