Table 1.
In vitro off-target binding assays and metabolic stability of IEM-1460 and IEM-1925.
| Radioligand binding assays | Antagonist: IEM-1925 (1 μM) | Antagonist: IEM-1460 (1 μM) | Liver microsome stability assays | Half-life (min) |
|---|---|---|---|---|
| Receptor/Channel | Mean% inhibition (N = 2) | Mean% inhibition (N = 2) | Mean (N = 2) | |
| hERG potassium (Kv 11.1), human | <1 | <5 | ||
| NMDA glutamate, rat | <1 | <1 | Human | |
| AMPA glutamate (GluA2-containing), rat | 9.5 | <1 | IEM-1460 IEM-1925 |
>300 >300 |
| A1 adenosine GPCR, human | <1 | <1 | ||
| H1 histamine GPCR, human | <1 | <1 | Guinea pig | |
| H2 histamine GPCR, human | <1 | <1 | IEM-1460 IEM-1925 |
>300 >300 |
| H3 histamine GPCR, human | <5 | <1 | ||
| H4 histamine GPCR, human | <5 | <1 | ||
| M1 acetylcholine GPCR, human | <1 | <1 | Mouse | |
| M2 acetylcholine GPCR, human | <1 | <1 | IEM-1460 IEM-1925 |
>300 >300 |
| M3 acetylcholine GPCR, human | <5 | 15 | ||
| M4 acetylcholine GPCR, human | 19 | 37 | ||
| M5 acetylcholine GPCR, human | <5 | 5.2 | ||
| nAChR alpha4/beta2, human | <1 | <1 | ||
| nAChR alpha7, human | <2 | <1 |
Left: Radioligand binding assays show% inhibition of binding of the receptor-specific radioligand (see Methods) to the off-target ion channel or receptor by 1 μM IEM-1460 or IEM-1925. Right: Stability of 1 μM IEM-1460 or IEM-1925 in the presence of mouse, guinea pig, or human liver microsomes at 37°C.