Relative induction of the γ-globin gene promoter by test compounds. (A) GM979 cells containing the integrated cassette (μLCRβ_prR_luc^Aγ_prF_luc) were assayed for luciferase activity. The ratio of firefly to renilla luciferase is shown for each compound tested: control, arginine butyrate (AB, 2500 μM), RB7 (200 μM), and RB25 (200 μM). Results are reported as relative induction and represent the mean of 4 experiments. Error bars indicate the standard errors of the mean. (B) γ-Globin mRNA induction in adult peripheral blood. Relative γ-globin mRNA expression levels (normalized to β-actin and G3PD transcripts) from cultured adult erythroid cells are shown in untreated control cells (C), or cells cultured with 100 μM arginine butyrate (AB) or 20 μM RB7. γ-Globin mRNA was induced 1.4-fold above control levels in cells cultured with AB, and 6.5-fold above control levels in cells treated with RB7. (C) Induction of fetal globin mRNA by RB7 treatment in an anemic baboon in vivo. Ratios of γ/γ+β-globin mRNA were induced by 2.8-fold and 4-fold above the animal's baseline level after 1 and 2 doses of RB7, respectively. The drug was administered on day 0 and day 5, as indicated by the solid bars above the graph. Insert shows baseline and on-treatment levels of γ-globin mRNA and 18S RNA.