科研之友
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摘要
Celastrol, the major bioactive ingredient isolated from Tripterygium wilfordii Hook F., is being developed as a promising anti-tumor drug. Given that anti-tumor drugs can be administered in combination with many drugs with narrow therapeutic windows, the potential drug-drug interaction risk due to the inhibition of UDP-glucuronosyltransferase (UGT) 1A3 might exist. Recombinant UGT1A3-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was used for evaluation of celastrol towards the activity of UGT1A3. Data fitting using Dixon plot and Lineweaver-Burk plot showed that celastrol is a competitive inhibitor of UGT1A3, and the second plot using the slopes of Lineweaver-Burk plot versus concentrations of celastrol was employed to calculate the inhibition kinetic parameter (K-i) to be 0.1 mu M. Due to the high concentration (10-100 fold as the Ki value) of celastrol needed to reach effective anti-tumor therapy, the high risk of drug-drug interaction exists between celastrol and drugs mainly undergoing UGT1A3-mediated metabolic elimination. All these results remind us that drug-drug interaction should be paid much attention when developing celastrol as a promising anti-tumor agent.
- 出版日期2012
- 单位烟台毓璜顶医院
