Lung Cancer Drug-Drug Interaction (DDI) Related with Praeruptorin D

Lung cancer is the leading cause of cancer death, and praeruptorin D (PD) is a drug candidate for the therapy of lung cancer. This study aims to determine lung cancer drug-drug interaction (DDI) related with PD through evaluating the inhibition capability of PD on the activity of phase II drug-metabolizing enzyme UDP-glucuronosyltransferases (UGTs). In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used as the probe reaction to determine the inhibition of PD on various isoforms of UGTs. PD 100 mu M exhibited no or not significant inhibition towards UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, and UGT2B7. In contrast, 100 mu M of PD showed strong inhibition on the activity of UGT2B15 (about 90% activity inhibited, p < 0.001) and UGT2B17 (about 80% activity inhibited, p < 0.001). In conclusion, the present study reported lung cancer DDI related with praeruptorin D via reporting the inhibition of the activity of UGT2B15 and UGT2B17. UGT2B17.