Screening of non-steroidal anti-inflammatory drugs for inhibitory effects on the activities of six UDP-glucuronosyltransferases ( XXXX , 1A3, 1A4, 1A6, 1A9, and 2B7) using LC-MS/MS.

@entity1 @entity32 @entity6912 @entity5230 @entity43923 @entity7988 @entity3522 @entity3785 @entity5018 @entity1443 @entity7987 @entity52084 @entity1623 @entity7154 @entity6900 @entity158 @entity11464 @entity9213 @entity22642
UNASSIGNED: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve @entity158 and decrease @entity32 . Several clinical studies have reported that NSAIDs inhibit @entity6900 ( @entity6900 ) enzymes. Therefore, we evaluated the inhibitory potential of 15 NSAIDs on the activities of six @entity6900 isoforms (i.e., @entity6912 , 1A3, 1A4, 1A6, 1A9, and 2B7) in @entity1 liver microsomes (HLMs). Among the 15 NSAIDs tested here, @entity7154 and @entity3522 inhibited all UGTs tested in this study. @entity5230 and @entity7987 inhibited @entity52084 activity (IC50    =   73.8    M and 0.38    M, respectively) and @entity1623 selectively inhibited @entity22642 activity (IC50    =   53.1    M), whereas it did not inhibit the other UGTs tested (IC50    >   200    M). Diflunisal inhibited the @entity6912 (IC50    =   33.0    M) and @entity52084 (IC50    =   19.4    M). @entity1443 , @entity43923 , @entity5018 , @entity7988 , @entity9213 , @entity11464 , @entity3785 , and sulindac showed negligible inhibitory effects on the six UGTs (IC50    >   100    M). These results suggest that some NSAIDs have the potential to inhibit UGTs in vitro. This article is protected by copyright. All rights reserved.
