TABLE 1.
XAF‐1407 in vitro pharmacology
| Recombinant ion channel | Equivalent cardiac current | IC50 (95% CI) | Hill coefficient (n H) | Selectivity ratio for Kir3.1/3.4 |
|---|---|---|---|---|
| Kir3.1/3.4 | I K,ACh | 0.0011 μM (0.0007–0.0018 μM) | 0.4 ± 0.04 | 1 |
| Kir3.4 | I K,ACh | 0.0032 μM (0.0025–0.0041 μM) | 0.4 ± 0.02 | ~3 |
| Kir2.1 | I K1 | >30 μM (12 ± 5% at 30 μM) | No fit possible | >27,000 |
| Kv11.1 (hERG) | I Kr | 4.2 μM (3.5–5.1 μM) | 0.9 ± 0.06 | ~3,800 |
| Nav1.5 (−100 mV/1 Hz) | I Na, peak | 8.8 μM (8.1 to 9.5 μM) | 2.2 ± 0.2 | 8,000 |
| Nav1.5 (−100 mV/5 Hz) | 5.3 μM (4.4 to 6.5 μM) | 1.8 ± 0.2 | >4,000 | |
| Nav1.5 (−70 mV/1 Hz) | 4.3 μM (3.8 to 4.8 μM) | 1.3 ± 0.1 | >4,000 | |
| Nav1.5 (−70 mV/5 Hz) | 2.6 μM (4.4 to 6.5 μM) | 1.4 ± 0.3 | >2,000 | |
| Kv1.5 | I Kur | 5.8 μM (4.7–7.1 μM) | 1.0 ± 0.08 | >5,000 |
| Kv4.3 | I to,1 | >10 μM (31 ± 7% at 10 μM) | ND | >9,000 |
| Kv7.1/KCNE1 | I Ks | 17 μM (13.8–21 μM) | 1.2 ± 0.15 | >15,000 |
| Kir6.2/SUR2A | I KATP | >10 μM (17 ± 13% at 10 μM) | ND | >9,000 |
| Cav1.2 | I Ca,L | >10 μM (5.8 ± 7.5% at 10 μM) | No fit possible | >9,000 |
Note: Summary of ion channel pharmacology of XAF‐1407 (in vitro): current or fluorescence (Cav1.2 only) inhibition data over a range of drug concentrations were fitted with a sigmoidal function to determine an IC50 and Hill coefficient (n H). Except Kv4.3 and Kir6.2/SUR2A where only a single concentration of 10 μM was tested.
Abbreviations: CI, confidence interval; ND, not determined.