Table 2.
Preclinical compounds active (IC50 < 50 μM) in hCx43 assay together with preclinical assessment data
| Compound | hCx43 IC50 (μM) n = 3 | hNaV1.5 IC50 (μM) | hCx43 : hNaV1.5 ratioa | In vivo species | Highest Cmax (total) (μM) | Cmax (free) (μM) | IC50 : Cmax (free) ratiob | QRSc | |
|---|---|---|---|---|---|---|---|---|---|
| hCx43 | hNaV1.5 | ||||||||
| C1 | 9 | 49 | 5.4 | Guinea pig | 54 | 5.4 | 1.7 | 9.1 | Yes |
| C2 | 13 | 30 | 2.3 | Guinea pig | 34 | 1.0 | 13 | 30 | Yes |
| C3 | 27 | >50 | >1.9 | Dog | 0.23 | 0.016 | >100 | >100 | No |
| C4 | 31 | 20 | 0.6 | Dog | 6 | 0.1 | >100 | >100 | Yes |
| C5 | 32 | 29 | 0.9 | Dog | 10 | 1.1 | 29 | 26 | No |
| C6 | 33 | 13 | 0.4 | Dog | 5 | 1.1 | 30 | 12 | Yes |
| C7 | 37 | 11 | 0.3 | Dog | 16 | 0.05 | >100 | >100 | Yes |
a
hCx43 : hNaV1.5 ratio is the ratio between hCx43 and hNaV1.5 IC50 values.
b
IC50 : Cmax (free) ratio is the ratio between the hCx43 or hNaV1.5 IC50 values and the compound free plasma concentration [Cmax (free)].
c
Indicates whether QRS prolongation was noted in the in vivo study.