Table 4. Profiling of Compound 18.
| assay | 18 | INCB-24360 (epacadostat) |
|---|---|---|
| enzymatic IDO1 IC50 (nM) | 63 | 26 |
| enzymatic TDO IC50 (nM) | 62 457 | >10 000 |
| cellular HeLa IC50 (nM) | 45 | 5.3 |
| CYP inhibition (1A2, 2C9, 2C19, 2D6, 3A4) | >10uM | >10uM |
| hERG | >30 uM | >30 uM |
| PPB (rat/dog/human) | 92.4%/96.0%/96.4% | 97.0%/97.5%/98.5% |
| liver microsome stability (rat/human) T1/2 (min) | 93.4/348.7 | 73.1/293 |
| mouse PK@3mg/kg | ||
| Cmax (ng/mL) | 127 | 253 |
| AUC (ng/mL·h) | 358 | 1016 |
| t1/2 (h) | 1.21 | 2.41 |
| Cl (μL/min/mg) | 61.2 | 49.2 |
| bioavailability (F%) | 44% | 44% |
| rat PK@3mg/kg | ||
| Cmax (ng/mL) | 179 | 133 |
| AUC (ng/mL·h) | 1527 | 807 |
| t1/2 (h) | 6.14 | 2.73 |
| Cl (μL/min/mg) | 16.7 | 29 |
| bioavailability (F%) | 58.8% | 55% |
| dog PK@2mg/kg | ||
| Cmax (ng/mL) | 742 | 245 |
| AUC (ng/mL·h) | 3633 | 676 |
| t1/2 (h) | 3.04 | 5.03 |
| Cl (μL/min/mg) | 9.3 | 36.6 |
| bioavailability (F%) | 102.1% | 50% |