Table 6. MrgX2 Selectivity and In Vitro DMPK Properties of Selected Compounds.
| Intrinsic
Clearance (mL/min/kg)c |
Plasma
Protein Binding (%fu)b |
|||||
|---|---|---|---|---|---|---|
| Cmpd | hCLINT | hCLHEPa | mCLINT | mCLHEPa | Human | Mouse |
| 1 | 61.9 | 15.2 | 1065 | 83.1 | 0.4 | 1.7 |
| 5c | 115.6 | 17.1 | 4888.6 | 88.5 | <0.3 | 1.5 |
| 5d | 40.2 | 13.4 | 979.1 | 82.5 | 0.4 | 2.2 |
| 5r | 74.9 | 15.8 | 1457.3 | 84.9 | <0.3 | 2.6 |
| 6b | 80.0 | 16.1 | 1210.7 | 83.9 | 0.5 | 2.1 |
| 6c | 79.1 | 16.0 | 1659 | 85.5 | 0.4 | 2.2 |
| 7a | 75.1 | 15.9 | 410.2 | 73.9 | 0.3 | 4.3 |
| 7e | 45.4 | 13.9 | 383.2 | 72.9 | 0.4 | 4.1 |
| 7g | 36.0 | 12.9 | 269.0 | 67.5 | 0.2 | 4.1 |
| 7i | 129.2 | 17.4 | 1470.4 | 85.0 | 0.1 | 0.1 |
| 8a | 138.4 | 17.6 | >2400 | >86.8 | 0.1 | 0.3 |
| 8c | 114.3 | 17.1 | 1101.6 | 83.3 | 0.3 | 1.2 |
| 8d | 69.3 | 15.6 | 1004.3 | 82.7 | 0.3 | 1.4 |
| 8e | 59.4 | 15.0 | 979.5 | 82.5 | 0.2 | 1.1 |
| 8f | 69.1 | 15.6 | 1235.7 | 84.0 | 0.2 | 0.1 |
a
Predicted hepatic clearance based on intrinsic clearance in human and mouse liver microsomes using the well-stirred organ CL model (binding terms excluded).
b
%fu = percent fraction unbound.
c
In vitro DMPK studies were performed at Q2 Solutions, Indianapolis, IN.