In silico profiling, Lipinski “Rule of 5” violations |
<2 |
0 |
0 |
0 |
In vitro potency (IC50, nM, W2 strain) |
<2000 |
<100 |
5.6 |
17.3 |
Bacterial mutagenicity, AMES test |
<3-fold increase in mutagenicity |
no increase in mutagenicity |
no increase in mutagenicity |
no increase in mutagenicity |
Metabolic stability, t½ human microsomes |
>0.5 h |
>4 h |
1.5 h (1 μM), 4.6 h (10 μM) |
0.80 h (1 μM), 1.8 h (10 μM) |
Permeability, PAMPA pH 7.4/7.4sink
|
>100 × 10-6 cm/s |
>1000 × 10-6 cm/s |
2400 × 10-6 cm/s |
1109 × 10-6 cm/s |
In vitro P450 inhibition (inhibition of CYP isoforms at 1μM concentration) |
Only CYP2D6 |
none |
none significant |
none significant |
Cytotoxicity, primary rat hepatocytes, ratio TC50 to IC50 W2 |
>20 |
>100 |
1340 |
2313 |
t1/2 (h, rodent) |
>2 |
>8 |
6.8 |
15.9 |
Cmax (nM, rodent) |
>80 |
>200 |
240 |
436 |
AUC (nmoles*h/L, rodent) |
>300 |
>1000 |
2026 |
6792 |