Table 2.
Kinetically derived parameters from the in vitro non-equilibrium binding kinetic data and the in vivo derived EC50
| In vitro kinetic parameters | Dissociation half-life (h) | In vivo | |||
|---|---|---|---|---|---|
| Compound | Kd (nM) | kon (M−1·min−1) | koff (min−1) | EC50 (nM) | |
| SN003 (tracer) | 3.64 ± 0.59 | 7.72e6± 1.6e6 | 0.026 ± 0.004 | 0.44 | ND |
| SN003 | 5.62 ± 0.53 | 6.2e6± 8.9e5 | 0.033 ± 0.004 | 0.35 | ND |
| PF-4325743 | 8.22 ± 1.48 | 4.06e6± 4.6e5 | 0.0316 ± 0.004 | 0.37 | ND |
| PF-4659901 | 4.24 ± 1.2 | 7.88e6± 1.8e6 | 0.028 ± 0.008 | 0.41 | ND |
| PF-4734666 | 3.06 ± 0.39 | 4.6e6± 5.1e5 | 0.0146 ± 0.003 | 0.79 | 13.4 ± 0.002 |
| DMP904 | 0.275 ± 0.07 | 1.47e7± 1.4e6 | 0.0038 ± 0.001 | 3.04 | ND |
| R121919 | 0.549 ± 0.15 | 3.69e6± 6.1e5 | 0.0019 ± 0.0005 | 6.08 | 0.290 ± 0.0003 |
| PF-4850890 | 0.734 ± 0.17 | 2.79e6± 6.4e5 | 0.0017 ± 0.0002 | 6.79 | 1.48 ± 0.002 |
Mean values ± SEM; n = 5–7 per compound.
Kd = equilibrium dissociation constant, kon = association rate constant, koff = dissociation rate constant, Dissociation half life = time for half the compound to dissociate from the receptor (calculated by ln2/koff), EC50 = concentration that causes 50% occupancy in vivo, ND = not determined.