Data Input | Molecules | Designation in Model | Value (Human) | Value (Dog) |
---|---|---|---|---|
Fraction of MRK-1 parent eliminated to M1 | MRK-1, M1 | f_p_m1 | 0.93 | 0.44 |
Fraction of MRK-1 parent eliminated to M2 | MRK-1, M2 | f_p_m2 | 0.02 | 0.04 |
Fraction of MRK-1 parent eliminated to inactive metabolites* | MRK-1 | f_p_xxx | 0.05 | 0.52 |
Fraction of M1 eliminated to M2 | M1, M2 | f_m1_m2 | 0.08 | 0.00 |
Fraction of M1 eliminated to inactive metabolites* | M1 | f_m1_xxx | 0.92 | 1.00 |
Fraction of M2 eliminated to M1 | M1, M2 | f_m2_m1 | 0.73 | 1.00 |
Fraction of M2 eliminated to inactive metabolites | M2 | f_m2_xxx | 0.27 | 0.00 |
ka | MRK-1 | Kap | 1.0/h | 2.9/h |
Fabs | MRK-1 | fabs | 1.0 | 1.0 |
CL | MRK-1 | CLp | 4.8 ml/min/kg | 10.1 ml/min/kg |
CL | M1 | CLm1 | 1.9 ml/min/kg | 1.6 ml/min/kg |
CL | M2 | CLm2 | 8.6 ml/min/kg | 17.7 ml/min/kg |
Volume of distribution | MRK-1 | V1p | 2.3 l/kg | 1.0 l/kg |
Volume of distribution | M1 | V1m1 | 1.6 l/kg | 1.1 l/kg |
Volume of distribution | M2 | V1m2 | 2.6 l/kg | 2.1 l/kg |
Elimination rate constant* | MRK-1 | kep | 0.125/h | 0.61/h |
Elimination rate constant* | M1 | kem1 | 0.071/h | 0.087/h |
Elimination rate constant* | M2 | kem2 | 0.198/h | 0.51/h |
Fraction unbound in plasma | MRK-1 | fup | 0.129 | 0.120 |
Fraction unbound in plasma | M1 | fum1 | 0.238 | 0.238 |
Fraction unbound in plasma | M2 | fum2 | 0.209 | 0.190 |
In vitro target binding potency | MRK-1 | p_IC50 | 1.2 nM | NA |
In vitro target binding potency | M1 | m1_IC50 | 1.8 nM | NA |
In vitro target binding potency | M2 | m2_IC50 | 0.7 nM | NA |
Molecular weight | MRK-1 | mwp | 324.38 Da | 324.38 Da |
Molecular weight | M1 | mwm1 | 296.33 Da | 296.33 Da |
Molecular weight | M2 | mwm2 | 338.36 Da | 338.36 Da |
Target unbound exposure for efficacy | MRK-1, M1, M2 | TargAUCuUM410equivs | 16.8 μM/h | NA |
NA, not applicable to model qualification.
↵* Values calculated within the model.