UGT Isoform | Specific Substrate | Reported HLM Unbound Km or S50 in µM (Vmax - pmol/min per mg) | Inhibitor | Reported IC50 (µM) | Inhibitor Reference |
---|---|---|---|---|---|
1A1 | SN-38 (active metabolite of irinotecan), a bit of 1A7 | 1.4 (820) without 2% BSA | Atazanavir | 1.9 | (Zhang et al., 2005; Liu et al., 2010) |
β-Estradiola,* | 6.6 (1400) with 2% BSA (β-estradiol-3-glucuronide) | Erlotinib | 1.2 (Ki = 0.64) | ||
1A3 | Zolarsartan (Alonen et al., 2008), fulvestrant (Chouinard et al., 2006), hexafluoro-1α, 25−dihydroxyvitamin D3 (Kasai et al., 2005) | Buprenorphine | 40–50 | (Oechsler and Skopp, 2010) | |
1A4 | Imipramine (Uchaipichat et al., 2006a) | 11 (1500) without 2% BSA | Hecogenin | 1.5 | (Uchaipichat et al., 2006a) |
Trifluorperazinea,* | 4.1 (870) with 2% BSA (trifluoperazine-N-glucuronide) | ||||
1A6 | Serotonin (Krishnaswamy et al., 2004) | 390 (66,000) without 2% BSA | Troglitazone | 20 | (Ito et al., 2001) |
5-Hydroxytryptophola,* | 300 (47,000) with 2% BSA (5HTOL-O-glucuronide) | ||||
1A7 (extrahepatic) | Octylgallate | Phenylbutazone(nonselective) | 3.9 | (Uchaipichat et al., 2006a) | |
1A8 (extrahepatic) | Dihydroxytestosterone metabolized to a diglucuronide (Murai et al., 2006) | Emodinb | 15.6 | (Watanabe et al., 2002) | |
1A9 | Propofola,* | 98 (1400) without 2% BSA | Niflumic acid | 0.0275 | (Mano et al., 2006) |
7.8 (780) with 2% BSA (propofol-O-glucuronide) | |||||
1A10 (extrahepatic) | Dopamine (Itaaho et al., 2009) | Tacrolimus | 0.034 | (Zucker et al., 1999) | |
2B7 | 3′-Azido-3′deoythymidine (AZT)a,* | 420 (2100) without 2% BSA | Fluconazolec | 146 (Ki = 73) | (Uchaipichat et al., 2006b) |
100 (4700) with 2% BSA (AZT-5′-glucuronide) | |||||
2B15 | (S)-Oxazepamd,* | 54 (303) without BSA [(S)-oxazepam glucuronide] | Ibuprofen | 120 | (Sten et al., 2009) |
SN-38, N-[(2′-dimethylamino)ethyl]acridine-4-carboxamide.
↵a Substrate and data acquired from Walsky et al. (2012a).
↵b 1A10 interaction may influence specificity assessment.
↵c Plus BSA in incubation.
↵d Substrate and data acquired from Court et al. (2002).
↵* Indicates the substrates which have been shown to be specific for each isoform, hence are the preferred tool compounds for UGT phenotyping.