Table 1.
ADME properties and cytotoxicity of BT13.
| Parameter | Species | ||
|---|---|---|---|
| Rat | Mouse | Human | |
| Vd (L/kg) | 23.55 | N/D | N/D |
| Clearance (L/h) | 4.7 | N/D | N/D |
| t1/2 (h) | 3.47 | N/D | N/D |
| Plasma stability (% remaining after 1 h) | 108.4 ± 7.3 | 110.3 ± 3.1 | 97.0 ± 0.1 |
| Microsomal stability (% remaining in 30 min) | 2.8 ± 0.1 | N/D | N/D |
| BBB penetration (%) | 55–68% | N/D | N/D |
| hERG inhibition (Ki, μM) | N/D | N/D | >30 |
| Cytotoxicity to human hepatoma cells (HepG2; LD50, μM) | N/D | N/D | 90.4 ± 8.5 |
| INHIBITION OF CYP ISOFORMS (IC50, μM) | |||
| CYP1A2 | N/D | N/D | >100 |
| CYP2C9 | N/D | N/D | >100 |
| CYP2C19 | N/D | N/D | >100 |
| CYP2D6 | N/D | N/D | >100 |
| CYP3A4 | N/D | N/D | 3.2 ± 0.42 |
BBB, blood brain barrier; hERG, human Ether-à-go-go-Related Gene; LD50, lethal dose 50, the dose that kills 50% of cells; Ki, constant of inhibition; IC50, concentration at 50% inhibition; CYP, cytochrome P450. N/D, not done.