Polymorphisms in UGT1A9 were associated with reduced toxicity and increased response to irinotecan in cancer patients. UDP-glucuronosyltransferase (UGT) protein expression, glucuronidation activities for 7-ethyl-10-hydroxycamptothecin (SN-38), and probe substrates of the UGT1A9 and UGT1A1 were measured in 48 human livers to clarify the role of UGT1A9 variants on the in vitro glucuronidation of ...

O-Glucuronidation of 5-hydroxyrofecoxib is the major biotransformation pathway of rofecoxib in human, rat, and dog. The glucuronide conjugate is also involved in the reversible metabolism of rofecoxib in rat and human. Atypical bimodal phenomena were observed in their plasma concentration-time curves with a large variability among different human subjects. It is unclear which family members of ...

Acetaminophen (APAP) glucuronidation is thought to occur mainly by UDP-glucuronosyltransferases (UGT) in the UGT1A family. Interindividual variation in APAP glucuronidation is attributed in part to polymorphisms in UGT1As. However, evidence suggests that UGT2B15 may also be important. We evaluated, in a controlled feeding trial, whether APAP conjugation differed by UGT1A6 and UGT2B15 genotypes ...

The UDP-glucuronosyltransferases (UGTs) are a superfamily of membrane-bound enzymes whose active site is localized inside the endoplasmic reticulum. Glucuronidation using human liver microsomes has traditionally involved disruption of the membrane barrier, usually by detergent treatment, to attain maximal enzyme activity. The goals of the current work were to develop a universal method to glucu...

Bilirubin, an end product of heme catabolism, is primarily eliminated via glucuronic acid conjugation by UGT1A1. Impaired bilirubin conjugation, caused by inhibition of UGT1A1, can result in clinical consequences, including jaundice and kernicterus. Thus, evaluation of the ability of new drug candidates to inhibit UGT1A1catalyzed bilirubin glucuronidation in vitro has become common practice. Ho...

Bilirubin, an end product of heme catabolism, is primarily eliminated via glucuronic acid conjugation by UGT1A1. Impaired bilirubin conjugation, caused by inhibition of UGT1A1, can result in clinical consequences, including jaundice and kernicterus. Thus, evaluation of the ability of new drug candidates to inhibit UGT1A1catalyzed bilirubin glucuronidation in vitro has become common practice. Ho...

Uncontrolled cell proliferation is the hall mark of many cancers, and is typically manifested by a deregulation of the cell-division cycle. CDKs play critical roles in regulating cell cycle, apoptosis and cell differentiation. AG-024322 is a multitargeted CDK inhibitor that has been shown to induce cancer cell apoptosis and demonstrate significant antitumor activity in human tumor xenograft mod...

Bilirubin, an end product of heme catabolism, is primarily eliminated via glucuronic acid conjugation by UGT1A1. Impaired bilirubin conjugation, caused by inhibition of UGT1A1, can result in clinical consequences, including jaundice and kernicterus. Thus, evaluation of the ability of new drug candidates to inhibit UGT1A1catalyzed bilirubin glucuronidation in vitro has become common practice. Ho...

Bilirubin, an end product of heme catabolism, is primarily eliminated via glucuronic acid conjugation by UGT1A1. Impaired bilirubin conjugation, caused by inhibition of UGT1A1, can result in clinical consequences, including jaundice and kernicterus. Thus, evaluation of the ability of new drug candidates to inhibit UGT1A1-catalyzed bilirubin glucuronidation in vitro has become common practice. H...