Table 1.
Selectivity profiling of reference KATP activators.
| Compound | Structure | Kir6.1/SUR2B | Kir6.2/SUR1 | Kir6.2/SUR2A | |||
|---|---|---|---|---|---|---|---|
| EC50 (µM) | Efficacy (%) | EC50 (µM) | Efficacy (%) | EC50 (µM) | Efficacy (%) | ||
| Levcromakalim |
|
0.55 ± 0.29 (7) | 90 ± 6 (7) | >30 (7) | 0 (7) | 6.9 ± 2.2 (7) | 85 ± 11 (7) |
| Y-26763 |
|
0.075 ± 0.042 (6) | 96 ± 3 (6) | 4.1 ± 2.1 (7) | 98 ± 2 (7) | 1.3 ± 0.97 (7) | 71 ± 5 (7) |
| BMS-191095 |
|
>30 (5) | 0 (5) | 1.4 ± 0.95 (5) | 82 ± 10 (5) | >30 (6) | 0 (6) |
| Pinacidil |
|
1.1 ± 0.60 (6) | 76 ± 9 (6) | >30 (6) | 0 (6) | 17 ± 5.8 (6) | 73 ± 14 (6) |
| P1075 |
|
0.052 ± 0.024 (10) | 100 (10) | >30 (10) | 0 (10) | 0.51 ± 0.27 (10) | 100 (10) |
| ZM226600 |
|
0.15 ± 0.090 (5) | 87 ± 6 (5) | >30 (5) | 0 (5) | 2.8 ± 2.2 (5) | 54 ± 10 (5) |
| ZD0947 |
|
0.52 ± 0.22 (6) | 57 ± 2 (6) | >30 (6) | 0 (6) | 11 ± 5.9 (6) | 33 ± 9 (6) |
| A-278637 |
|
0.17 ± 0.089 (5) | 88 ± 6 (5) | >30 (6) | 0 (6) | 1.6 ± 0.89 (6) | 95 ± 4 (6) |
| NN414 |
|
>30 (9) | 0 (9) | 0.26 ± 0.16 (9) | 100 (9) | >30 (9) | 0 (9) |
| Diazoxide |
|
9.7 ± 5.7 (7) | 38 ± 9 (7) | 6.2 ± 4.8 (7) | 97 ± 5 (7) | >100 (7) | 0 (7) |
| VU0071063 |
|
>30 (5) | 0 (5) | 1.1 ± 0.62 (6) | 100 ± 1 (6) | >30 (6) | 0 (6) |
Functional properties of KATP channel activators were characterized at human Kir6.1/SUR2B, Kir6.2/SUR1, and Kir6.2/SUR2A channels stably expressed in HEK293 cells. Fitted efficacy levels were normalized to the maximal efficacy obtained with P1075 (Kir6.1/SUR2B and Kir6.2/SUR2A) and NN414 (Kir6.2/SUR1). The values are given as mean ± S.D. and the number of individual experiments (each performed in quadruplicate) are in parentheses (n).