Inhibition of UGT by PF-06409577 and ES in the absence of 2% BSA
The ES UGT1A1 HLM IC50 values used the following probe substrates: 5-(4-hydroxyphenyl)-5-phenylhydantoin, bergenin, etoposide, niflumic acid, puerarin, raltegravir, T5224, and troglitazone. The ES hrUGT1A9 IC50 values were generated using 4-methylumbelliferone and scopoletin as the probe substrate.
| UGT Isoform | PF-06409577 C50 and 95% CI | ES IC50 and 95% CI |
|---|---|---|
| µM | µM | |
| 1A1 | 24 (20.6–27.2) | 4.21–261a |
| 1A4 | >100 | N.D. |
| 1A6 | >100 | N.D. |
| 1A9 | 41.3 (30.5–55.9) | 2.1a |
| 2B7 | >100 | 4.37 (3.97–4.80) |
CI, confidence interval; N.D., not determined.
↵a The IC50 values were obtained from the University of Washington Drug Interaction Database (https://didb.druginteractioninfo.org/query/enzyme/precipitants-affecting-enzyme/?QueryId=12&EnzymeOid=82&EffectId=0).