Table 5.
Summary of 26 (VU0418506)
 26, VU0418506 | |
|---|---|
| human mGlu4 EC50 (nM) | 68 nM |
| rat mGlu4 EC50 (nM) | 46 nM |
| rat fold shift (@30 µM) | 15.5 |
| MW | 262.7 |
| cLogP | 3.96 |
| TPSA | 53.6 |
| intrinsic clearance (mL/min/kg) | |
| human CLHEP | 10.1 |
| rat CLHEP | 12.1 |
| dog CLHEP | 18.9 |
| mouse CLHEP | 50.1 |
| rhesus CLHEP | 11.5 |
| plasma protein binding (%Fu) | |
| human | 1.7 |
| rat | 2.8 |
| dog | 0.9 |
| mouse | 1.9 |
| rhesus | 1.4 |
| CYP450 inhibition (µM) | |
| 1A2 | <0.1 |
| 2C9 | 8.9 |
| 2D6 | >30 |
| 3A4 | >30 |
| 2C19 | 6.1 |
| in vivo PK parameters (rat IV, 1 mg/kg) | |
| CL (mL/min/kg) | 29 |
| Vss (L/kg) | 4.0 |
| AUC (ng·h/mL) | 608 |
| MRT (min) | 132 |
| t1/2 (min) | 91 |
| in vivo PK parameters (rat PO, 10 mg/kg) | |
| Cmax (ng/mL) | 875 |
| Tmax (h) | 2 |
| AUC PO (ng·h/mL) | 7418 |
| %F | 95% |
| rat CNS PO PBL (0−6 h) | |
| plasma (ng·h/mL) | 8771 |
| brain (ng·h/mL) | 18 415 |
| B:P | 2.1 |
| Papp, A−B (10−6) | 24 |
| Papp, B−A (10−6) | 14 |
| efflux ratio | 0.6 |