Table 1.

Overview of the newly identified transporters of iodothyronines and/or iodothyronine sulfates in mouse and human SLC22 family. For the specificity and efficacy of lesinurad and probenecid, IC50 values were listed. SLC22A9, SLC22A11 and SLC22A24 are human specific, whereas SLC22A19, SLC22A26-30 are mouse specific.

	Mouse					Human
Transporter	Substrates	Expression in tissuesa	Substrate tested for inhibition	Lesinurad IC50	Probenecid IC50	Substrates	Expression in tissuesb	Substrate tested for inhibition	Lesinurad IC50	Probenecid IC50
SLC22A8	3,3'-T2, rT3, T3, T4, T3S, T4S	Kidney, frontal lobe, brain (endothelial cells)c	T4	1.3 μM	6.0 μM	3,3'-T2, rT3, T3, T4, T3S, T4S	Kidney, choroid plexus	T3S	0.6 μM	3.5 μM
SLC22A9	Not in mouse					T3, T4, T3S, T4S	Liver	T3S	50 μM	413 μM
SLC22A11	Not in mouse					T4, T3S	Placenta, kidney, epididymis	T4	8.8 μM	57 μM
SLC22A19	T4	Kidney	T4	5.4 μM	773 μM	Not in human
SLC22A24	Not in mouse					T4	Kidney	T3Sd	11 μM	24 μM
SLC22A26	rT3, T4, T4S	Liver	T4	17 μM	x	Not in human
SLC22A27	3, 3'-T2, rT3, T3, T4, T3S, T4S	Liver	T4	x	x	Not in human
SLC22A28	T3, T4	Liver, kidney	T4	26 μM	>>1000 μM	Not in human
SLC22A29	rT3, T3, T4, T3S, T4S	Kidney	T4	x	x	Not in human
SLC22A30	T3, T4	Liver	T4	x	x	Not in human

^aThe tissue expression in mouse was adopted from the mouse ENCODE transcriptome data project (‘A comparative encyclopedia of DNA elements in the mouse genome’ by Yue et al. in 2014) (34). Expression less than five reads per kilo base per million mapped reads (RPKM) are neglected; ^bThe tissue expression in human was adopted from the HPA datasets from https://www.proteinatlas.org/. Expression less than three transcripts per million (TPM) are neglected; ^cCell-specific expression in brain was adopted from http://www.brainrnaseq.org/; ^dT3S was used as the substrate to test for inhibition effect because hSLC22A24 induced T3S uptake more robustly though the induction did not reach statistical significance.

>>1000 μM means within the tested doses, IC50 was not reached; N.T., not tested; X, no inhibition effect.