IC50 values for inhibition of human UDP-glucuronosyltransferases by amitriptyline, androsterone, canrenoic acid, hecogenin, phenylbutazone, quinidine, quinine, and sulfinpyrazone
UGTa | IC50b | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Amitriptyline | Androsterone | Canrenoic Acid | Hecogenin | Phenylbutazone | Quinidine | Quinine | Sulfinpyrazone | ||||||||
| μM | |||||||||||||||
| 1A1 | 1345 ± 37 | 125 ± 6 | 372 ± 1 | N.D.c | 294 ± 4 | 776 ± 14 | 861 ± 7 | 46 ± 1.6 | |||||||
| 1A3 | 1120 ± 22 | 65 ± 31 | 1387 ± 27 | N.D.c | 266 ± 8 | N.D.d | 388 ± 41 | 267 ± 4 | |||||||
| 1A4 | 856 ± 24 | 106 ± 5 | 503 ± 24 | 1.5 ± 0.1 | 1227 ± 95 | 1619 ± 17 | 1355 ± 56 | 651 ± 13 | |||||||
| 1A6 | 152 ± 4 | N.D.c | 545 ± 20 | N.D.c | 10 ± 6 | 2515 ± 480 | 3290 ± 240 | 187 ± 11 | |||||||
| 1A7 | 355 ± 22 | N.D.c | 693 ± 30 | N.D.c | 11 ± 1.5 | 507 ± 10 | 970 ± 69 | 16 ± 2 | |||||||
| 1A8 | 111 ± 10 | N.D.d | 362 ± 4 | N.D.c | 40 ± 1.6 | 551 ± 13 | 977 ± 17 | 158 ± 1 | |||||||
| 1A9 | 443 ± 6 | 7 ± 4.2 | 1205 ± 53 | N.D.c | 13 ± 0.2 | 278 ± 20 | >5000 | 11 ± 0.7 | |||||||
| 1A10 | 153 ± 10 | 102 ± 4 | 318 ± 9 | N.D.c | 48 ± 1.8 | 536 ± 2 | 717 ± 18 | 58 ± 0.6 | |||||||
| 2B7 | 129 ± 4 | 16 ± 4 | 707 ± 25 | N.D.c | 2962 ± 727 | 159 ± 21 | 322 ± 11 | 2741 ± 45 | |||||||
| 2B15 | 72 ± 0.4 | 48 ± 3 | 249 ± 4 | N.D.c | 394 ± 6 | 133 ± 14 | 212 ± 4 | 402 ± 9 | |||||||
↵ a Basal control activities of UGT 1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7, and 2B15 at the substrate concentrations used (see Materials and Methods) were 65, 400, 300, 70,000, 15,000, 2800, 3000, 5300, 70, and 15 pmol/min · mg, respectively.
↵ b Data are presented as mean ± standard error of parameter fit.
↵ c N.D., not determined due to low degree of inhibition (IC50 > 200 μM).
↵ d N.D., not determined due to enzyme activation.