Research Article

FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors

Table 1

γ-globin induction in KU812-γF/βR stable lines by FK228 derivatives1.

Line 1Drug concentration Mean SEM valueFold change

Untreatednone0.04020.0091n/a1
Cys10 mM0.03880.00920.85280.950
Hemin50 μM0.17320.03990.00504.325
SAHA2000 nM0.21570.01420.00015.400
FK2281.5 nM0.11970.03250.01502.975
1127Ox1000 nM0.03630.00220.81670.900
JMA11.5 nM0.04730.01490.67201.175
JMA21.0 nM0.01570.00030.16290.400
JMA121000 nM0.01870.00090.21560.475
JMA26500 nM0.14600.02340.00043.650
JMA331000 nM0.13730.01170.00023.425
JMA112100 nM0.01870.00070.21562.453

Line 2Drug concentration Mean SEM valueFold change

Untreatednone0.15730.0150n/a1
Cys10 mM0.12000.00560.19770.764
Hemin50 μM0.65930.08390.00014.261
SAHA2000 nM0.65000.02080.00014.140
FK2281.5 nM0.61670.03380.00013.929
1127Ox1000 nM0.61330.03710.00013.904
JMA11.5 nM0.12600.01520.28960.803
JMA21.0 nM0.11830.00710.18140.752
JMA121000 nM0.14700.00270.70930.936
JMA26500 nM0.24870.03080.01531.579
JMA331000 nM0.33130.02560.00022.108
JMA112100 nM0.10700.00760.09380.682

Line 3Drug concentration Mean SEM valueFold change

Untreatednone0.07210.0052n/a1
Cys10 mM0.08600.00500.18141.194
Hemin50 μM0.25080.01530.00013.486
SAHA2000 nM0.25200.00660.00013.500
FK2281.5 nM0.15830.01980.00072.194
1127Ox1000 nM0.03700.00950.00760.514
JMA11.5 nM0.07700.00360.61791.069
JMA21.0 nM0.07400.00360.84631.027
JMA121000 nM0.05370.00230.07790.750
JMA26500 nM0.25600.01920.00013.555
JMA331000 nM0.51200.17650.00077.111
JMA112100 nM0.04670.00190.02160.653

1Using three independent KU812-γF/βR stable cell lines, the FK228 analogues were examined for their ability to induce γ-globin. After 48 hr drug treatments, cells were harvested and dual luciferase assay performed. Untreated cells were used as a control and normalized to one. Data were calculated as the means standard error of the mean (SEM).