Drug inhibition of 4-MUA hydrolysis by CES1A1 and CES2
4-MUA was incubated in the presence of varying inhibitors in 90 mM KH2PO4 and 40 mM KCl, pH 7.4. Formation of the product, 4-methylumbelliferone, was monitored spectrophotometrically at 350 nm. Data were fit to an inhibition model to estimate the IC50.
Inhibitor | CES1A1 IC50 (95% CI) | CES2 IC50 (95% CI) | |
|---|---|---|---|
| mM | |||
| Loperamide | 0.44 (0.36-0.53) | 3.8 × 10-4 | |
| (2.7 × 10-4-5.4 × 10-4) | |||
| Dolasetron mesylate | 0.33 (0.26-0.42) | 0.50 (0.36-0.70) | |
| Docetaxel | 0.68 (0.59-0.77) | 0.79 (0.62-1.0) | |
| Capecitabine | 4.9 (4.2-5.5) | 4.8 (4.1-5.5) | |
| Atropine | 7.0 (6.7-7.2) | 9.0 (8.5-9.5) | |
| Dexamethasone | N.D. | 22 (17-29) | |
N.D., not determined; 95% CI, 95% confidence interval.