Table 6. Profile of 51 and 59(12).
| 51 | 59 | |
|---|---|---|
| CDK8 IC50 ± SD (nM) | 5.1 ± 0.3 | 32.7 ± 2.1 |
| CDK8 residence time (min) ± SD | 15 ± 2 | 23 ± 3 |
| CDK19 IC50 ± SD (nM) | 5.6 ± 0.6 | 18.8 ± 1.4 |
| CDK19 residence time (min) ± SD | 31 ± 3 | 42 ± 5 |
| pSTAT1SER727 IC50 ± SD (nM) | 17.9 ± 10.6 | 114.0 ± 20.6 |
| 7dF3 IC50 ± SD (nM) | 7.2 ± 3.1 | 21.0 ± 1.6 |
| Clint (μL/min/mg) M/R/H | 52/26/61 | 38/18/<10 |
| mousePKa | ||
| Cl (L/h/kg) | 1.94 | 1.57 |
| Vss (L/kg) | 1.87 | 1.62 |
| F (%) | 18 | 15 |
| % in feces (iv dosing) | 31 | 18 |
| ratPKa | ||
| Cl (L/h/kg) | 1.29 | |
| Vss (L/kg) | 2.13 | |
| F (%) | 57 | |
| % in feces (iv dosing) | 36 |
a
Dose 0.2 mg/kg (iv), 0.5 mg/kg (po).