Table 2.

Comparison of published VKOR inhibition data

	Gebauer32	Tie et al34	Westhofen et al14	Tie et al35	Fregin et al36	Hammed et al17	Bevans et al33	Haque et al37	Present study	Present study	Present study
Expression system/cell line	Rat liver microsomes	HEK 293	HEK 293T	HEK 293 WT and C1 KO	HEK 293T	P. pastoris	P. pastoris	HEK 293-C3	C1 KO and L1 KO HEK 293T	C1 KO and L1 KO HEK 293T	DKO HEK 293T
VKOR expression	Endogenous	Endogenous	Overexpression of both VKOR enzymes	Endogenous	Overexpression of VKORC1	Overexpression of both VKOR enzymes	Overexpression of VKORC1	Endogenous	Endogenous	Endogenous	Overexpression of both VKOR enzymes
Type of measurement	Direct	Indirect	Direct	Indirect	Indirect	Direct	Direct	Indirect	Indirect	Indirect	Indirect
Activity measurement	K>O conversion	FIXgla-PC	K>O conversion	FIXgla-PC	FIX	K>O conversion	K>O conversion	F9CH	FIX	FIX	FIX
Reporter expression	NA	Stable	NA	Stable	Transient	NA	NA	Inducible, stable	Transient	Transient	Transient
Substrate	25 mM K1>O	5 µM K1>O	50 µM K1>O	5 µM K1>O	10 µM K1	Up to 0.2 mM K1>O	Up to 1 µM K1>O	50 nM K1	12 µM K1	12 µM K1>O	12 µM K1
Type of assay	DTT assay	ELISA	DTT assay	ELISA	Clotting assay	DTT assay	DTT assay	FACS	Clotting assay	Clotting assay	Clotting assay
Discrimination between C1 and L1	No	No	Yes (but remaining endogenous activity)	Yes (in KO cell line)	Yes (but remaining endogenous activity)	Yes	Yes	No	Yes	Yes	Yes
Warfarin	IC50 2.2 µM	IC50 100 nM	At 5 µM: C1: 53% inhibition L1: 29% inhibition	IC50 < 50 nM	IC50 25 nM	Ki ratios: hL1/C1: 29× rL1/C1: 54×	IC50 3-24 µM	IC50 125 nM	IC50: C1: 1.9 nM L1: 25.2 nM	IC50: C1: 2.4 nM L1: 27 nM	IC50: C1: 17.3 nM L1: 474 nM

Published data regarding inhibition of VKORC1 or VKORC1L1 by warfarin are summarized.

K_i, inhibitory constant.