EM-652 glucuronidation by human UGT1A1, UGT1A3, UGT1A8, and UGT1A9 and by monkey monUGT1A01, monUGT1A08, and monUGT1A09 before and after normalization for level of protein expression.
| Glucuronide Formation | ||||||
|---|---|---|---|---|---|---|
| EM-652-4′-G | Normalized | EM-652-7-G | Normalized | EM-652-G Total | Normalized | |
| pmol/min/mg of protein | ||||||
| Human | ||||||
| UGT1A1 | 5.3 ± 1.5 | 5.3 | 55.7 ± 12.7 | 55.7 | 61.0 ± 14.2 | 61.0 |
| UGT1A3 | 41.4 ± 1.5 | 82.8 | 28.6 ± 2.1 | 57.2 | 70.0 ± 3.6 | 140.0 |
| UGT1A8 | 30.7 ± 3.9 | 1.9 | 52.8 ± 3.9 | 3.3 | 83.5 ± 7.8 | 5.2 |
| UGT1A9 | 30.8 ± 13.5 | 1.9 | 31.3 ± 0.7 | 1.9 | 62.1 ± 14.2 | 3.8 |
| Monkey | ||||||
| UGT1A01 | 3.2 ± 0.2 | 3.2 | 9.0 ± 2.2 | 9.0 | 12.2 ± 2.4 | 12.2 |
| UGT1A08 | 55.9 ± 9.0 | 14.9 | 59.8 ± 6.4 | 16 | 115.7 ± 15.4 | 6.6 |
| UGT1A09 | 19.7 ± 2.2 | 15.5 | 116.2 ± 14.2 | 78.0 | 135.9 ± 16.4 | 93.5 |
The level of EM-652 glucurono-conjugation by UGT enzymes was determined for each hydroxyl position of the molecule by incubating microsomal proteins of UGT-HEK293 cells and EM-652 for 3 h. Values were normalized for the level of protein expression in stable expressing HEK293 cells. Expression of protein in UGT1A1- and monUGT1A01-HEK293 cells defined as reference values (expression = 1). Values represent the mean of three independent experiments ± S.D.