TABLE 1

Data inputs, designations in model script, and numerical values used for partial model qualification (dog) and prediction of MRK-1 efficacious dose (human)

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.