Table 2.

Potency of verinurad against human (h) URAT1 and rat (r) URAT1, and chimeric point mutants in TM1, TM7 and TM11.

	Human URAT1	Verinurad affinity (IC50, µM)	Rat URAT1	Verinurad affinity (IC50, µM)
Wild type	hURAT1	0.025 ± 0.0036	rURAT1	41 ± 2.7
TM1 point mutants	h-V18L	0.026 ± 0.015	r-L18V	40 ± 6.1
	h-T21A	0.026 ± 0.012	r-A21T	36 ± 5.2
	h-M22V	0.029 ± 0.013	r-V22M	43 ± 2.5
	h-M25V	0.029 ± 0.010	r-V25M	18 ± 3.2**
	h-V26T	0.014 ± 0.0015	r-T26V	39 ± 5.5
	h-S27P	0.039 ± 0.0090*	r-P27S	27 ± 3.4**
	h-M29L	0.011 ± 0.0029**	r-L29M	29 ± 3.3*
	h-L31V	0.031 ± 0.010	r-V31L	29 ± 3.2*
	h-C32T	0.095 ± 0.026****	r-T32C	29 ± 3.1*
	h-S35N	0.36 ± 0.15***	r-N35S	10 ± 1.5****
TM7 point mutant	h-F365Y	4.0 ± 1.7***	r-Y365F	2.9 ± 1.3****
TM11 point mutant	h-I481M	0.053 ± 0.010***	r-M481I	11 ± 3.1***

Values (mean ± SEM) are from at least three dose-response experiments as shown in Fig. 3. Asterisks indicate significant differences in mean values from the corresponding wild type transporter. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.