Table 1.
Selectivity against various splicing targets.
| Comp | EC1.5× (nM) | EC50 (nM) | EC4.0× (nM) | EC3.0× (nM) | EC50 (nM) | EC50 (nM) | Selectivity | Selectivity | Selectivity |
|---|---|---|---|---|---|---|---|---|---|
| FL-SMN2 | FOXM1b | FOXM1ΔC | FOXM1a | GALC | HTT | FOXM1b /FL-SMN2 |
GALC /FL-SMN2 |
HTT /FL-SMN2 |
|
| TEC-1 |
49.1 (22.7–109.4) |
> 3000.0 |
1311.6 (864.7–2285.8) |
1096.8 (809.7–1552.2) |
> 3000.0 | > 3000.0 | > 61 | > 61 | > 61 |
| Risdiplam |
15.8 (8.81–32.8) |
123.5 (93.2–160.4) |
38.9 (6.98–85.0) |
24.2 (4.49–78.5) |
N.T. | N.T. | 8 | N.T. | N.T. |
| SMN-C3 |
122.1 (74.5–221.7) |
945.2 (620.0–1349.0) |
298.5 (248.8–355.8) |
280.3 (211.4–377.7) |
459.4 (315.7–645.5) |
547.2 (373.6–771.3) |
8 | 4 | 4 |
The EC values were calculated for a 6-point titration curve using nonlinear regression with Graphpad Prism for compounds whose curves are shown in Figs. 1, 2, 3, or 4. GM03813 fibroblasts were exposed to each compound for 24 h. The amounts of each target mRNA were normalized to those of GAPDH. An EC1.5×, 4.0× or 3.0× value shows 50%, 300%, or 200% total target mRNA increase. An EC50 value of the target shows 50% total target mRNA reduction. The 95% confidence intervals are listed in brackets. To estimate selectivity, each EC value was divided with EC1.5× of FL-SMN2. N.T. indicates Not Tested.