FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors
Table 1
γ-globin induction in KU812-γF/βR stable lines by FK228 derivatives1.
Line 1
Drug concentration
Mean
SEM
value
Fold change
Untreated
none
0.0402
0.0091
n/a
1
Cys
10 mM
0.0388
0.0092
0.8528
0.950
Hemin
50 μM
0.1732
0.0399
0.0050
4.325
SAHA
2000 nM
0.2157
0.0142
0.0001
5.400
FK228
1.5 nM
0.1197
0.0325
0.0150
2.975
1127Ox
1000 nM
0.0363
0.0022
0.8167
0.900
JMA1
1.5 nM
0.0473
0.0149
0.6720
1.175
JMA2
1.0 nM
0.0157
0.0003
0.1629
0.400
JMA12
1000 nM
0.0187
0.0009
0.2156
0.475
JMA26
500 nM
0.1460
0.0234
0.0004
3.650
JMA33
1000 nM
0.1373
0.0117
0.0002
3.425
JMA112
100 nM
0.0187
0.0007
0.2156
2.453
Line 2
Drug concentration
Mean
SEM
value
Fold change
Untreated
none
0.1573
0.0150
n/a
1
Cys
10 mM
0.1200
0.0056
0.1977
0.764
Hemin
50 μM
0.6593
0.0839
0.0001
4.261
SAHA
2000 nM
0.6500
0.0208
0.0001
4.140
FK228
1.5 nM
0.6167
0.0338
0.0001
3.929
1127Ox
1000 nM
0.6133
0.0371
0.0001
3.904
JMA1
1.5 nM
0.1260
0.0152
0.2896
0.803
JMA2
1.0 nM
0.1183
0.0071
0.1814
0.752
JMA12
1000 nM
0.1470
0.0027
0.7093
0.936
JMA26
500 nM
0.2487
0.0308
0.0153
1.579
JMA33
1000 nM
0.3313
0.0256
0.0002
2.108
JMA112
100 nM
0.1070
0.0076
0.0938
0.682
Line 3
Drug concentration
Mean
SEM
value
Fold change
Untreated
none
0.0721
0.0052
n/a
1
Cys
10 mM
0.0860
0.0050
0.1814
1.194
Hemin
50 μM
0.2508
0.0153
0.0001
3.486
SAHA
2000 nM
0.2520
0.0066
0.0001
3.500
FK228
1.5 nM
0.1583
0.0198
0.0007
2.194
1127Ox
1000 nM
0.0370
0.0095
0.0076
0.514
JMA1
1.5 nM
0.0770
0.0036
0.6179
1.069
JMA2
1.0 nM
0.0740
0.0036
0.8463
1.027
JMA12
1000 nM
0.0537
0.0023
0.0779
0.750
JMA26
500 nM
0.2560
0.0192
0.0001
3.555
JMA33
1000 nM
0.5120
0.1765
0.0007
7.111
JMA112
100 nM
0.0467
0.0019
0.0216
0.653
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).