Novel valproic acid derivatives with hemoglobin F inducing activity.
Pharmacological induction of hemoglobin F expression may be a promising approach for the treatment of beta-thalassemia and sickle cell disease. Valproic acid, a drug frequently used for the treatment of seizure disorders, has been shown to enhance fetal hemoglobin synthesis in erythroid cells. However, this effect is only modest and requires relative high concentrations. Therefore, the drug appears not to be applicable for the treatment of beta-globin chain disorders. Here, we describe the identification of novel valproic acid derivatives with potent hemoglobin F inducing activities at concentrations that presumably can be obtained in vivo.
Rönndahl
G
G
Pediatrics I, Children's Hospital, University of Göttingen, Göttingen, Germany.
Mönkemeyer
S
S
Schulze
S
S
Pekrun
A
A
Eikel
D
D
Nau
H
H
Witt
O
O
D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005319:Fetal Hemoglobin / Q000096:biosynthesis*; D006801:Humans; D020014:K562 Cells; D013329:Structure-Activity Relationship; D014635:Valproic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
D014635:Valproic Acid; D005319:Fetal Hemoglobin