TABLE 2

Antagonist activity of AMG8379 and AMG8380 at human and mouse NaV channels

IC50 values are expressed as mean ± SEM. n = number of replicate experiments performed.

Channel3078379 IWQ IC50 (μM)3078380 IWQ IC50 (μM)
hNaV1.1>14 (n = 3)>14 (n =3)
hNaV1.22.17 ± 0.07a (n =3)> 30a (n =3)
hNaV1.3>14 (n =3)>14 (n =3)
hNaV1.4>14 (n =3)>14 (n =3)
hNaV1.5>14 (n =3)>14 (n =3)
hNaV1.61.31 ± 0.17 (n =4)>10 (n =6)
hNaV1.70.0032 ± 0.001 (n =5)0.391 ± 0.160 (n =6)
mNaV1.1> 30a (n =3)> 30a (n =3)
mNaV1.62.74 ± 0.49a (n =3)> 30a (n =3)
mNaV1.70.0168 ± 0.005 (n =4)0.681 ± 0.258 (n =7)
  • hNaV1.1, human NaV1.1; hNaV1.2, human NaV1.2; hNaV1.3, human NaV1.3; hNaV1.4, human NaV1.4; hNaV1.5, human NaV1.5; hNaV1.6, human NaV1.6; hNaV1.7, human NaV1.7; IWQ, IonWorks Quattro; mNaV1.1, mouse NaV1.1; mNaV1.6, mouse NaV1.6; mNaV1.7, mouse NaV1.7.

  • a Compound potency determined by manual patch-clamp electrophysiology using the IWQ voltage protocol.