Crigler-Najjar syndrome is a severe metabolic disease of the liver due to a reduced activity of the UDP Glucuronosyltransferase 1A1 (UGT1A1) enzyme. In an effort to translate to the clinic an adeno-associated virus vector mediated liver gene transfer approach to treat Crigler-Najjar syndrome, we developed and optimized a vector expressing the UGT1A1 transgene. For this purpose, we designed and ...

UNLABELLED Belinostat is a hydroxamate class HDAC inhibitor that has demonstrated activity in peripheral T-cell lymphoma and is undergoing clinical trials for non-hematologic malignancies. We studied the pharmacokinetics of belinostat in hepatocellular carcinoma patients to determine the main pathway of metabolism of belinostat. The pharmacokinetics of belinostat in liver cancer patients were c...

INTRODUCTION The UGT1A1*28 (rs8175347) polymorphism is associated with hyperbilirubinemia. The presence of 6 TA-repeats in the UGT1A1 gene promoter region corresponds to normal UGT1TA1 activity. A detection of 7 TA-repeats in hetero- or homozygous individuals [(TA)6/(TA)7 and (TA)7/(TA)7] is associated with lower UGT1TA1 activity, which may eventually result in the development of Gilbert syndro...

Background: FOLFIRI regimen, which is composed of 5-FU, Leucovorin, and Irinotecan, is used in the first-line chemotherapy of metastatic colorectal cancer. Irinotecan life threatening toxicity is partly related to cytotoxic drug metabolite which is primarily inactivated by the UGT1A1 enzyme. The primary aim of the present research was to find the correlation between UGT1A1-genotype and clinical...

Acyl glucuronidation is an important metabolic pathway for fluoroquinolone antibiotics. However, it is unclear which human UDP-glucuronosyltransferase (UGT) enzymes are involved in the glucuronidation of the fluoroquinolones. The in vitro formation of levofloxacin (LVFX), grepafloxacin (GPFX), moxifloxacin (MFLX), and sitafloxacin (STFX) glucuronides was investigated in human liver microsomes a...

Several human immunodeficiency virus (HIV) protease inhibitors, including atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir, were tested for their potential to inhibit uridine 5'-diphospho-glucuronosyltransferase (UGT) activity. Experiments were performed with human cDNA-expressed enzymes (UGT1A1, 1A3, 1A4, 1A6, 1A9, and 2B7) as well as human liver microsomes. All of the p...

A metabolite formed by incubation of human liver microsomes, etoposide, and UDP-glucuronic acid was identified as etoposide glucuronide by liquid chromatography-tandem mass spectrometry analysis. According to the derivatization with trimethylsilylimidazole (Tri-Sil-Z), it was confirmed that the glucuronic acid is linked to an alcoholic hydroxyl group of etoposide and not to a phenolic group. Am...

Chemoprevention by isothiocyanates from cruciferous vegetables occurs partly through up-regulation of phase II conjugating enzymes, such as UDP-glucuronosyltransferases (UGT). UGT1A1 glucuronidates bilirubin, estrogens, and several dietary carcinogens. The UGT1A1*28 polymorphism reduces transcription compared with the wild-type, resulting in decreased enzyme activity. Isothiocyanates are metabo...

Human UDP-glucuronosyltransferase (UGT) 1A1 is a critical enzyme responsible for detoxification and metabolism of endogenous and exogenous lipophilic compounds such as bilirubin. The present study shows how cyclin-dependent kinase (CDK) inhibitor roscovitine stimulated the expression of UGT1A1 in HepG2 cells. Pregnane X receptor (PXR)-mediated transactivation of UGT1A1 reporter gene was more pr...