Inhibition of human UDP-glucuronosyltransferase enzymes by lapatinib, pazopanib, regorafenib and sorafenib: Implications for hyperbilirubinemia
| Autor: | Nuy Chau, Kushari Burns, John O. Miners, Ross A. McKinnon, Kathleen M. Knights, Andrew Rowland, Geoffrey T. Tucker, Peter I. Mackenzie, Ganessan Kichenadasse |
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| Rok vydání: | 2017 |
| Předmět: |
Niacinamide
Sorafenib Indazoles UGT1A4 Pyridines Bilirubin Glucuronidation Pharmacology Lapatinib digestive system 030226 pharmacology & pharmacy Biochemistry Catalysis Pazopanib 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Regorafenib medicine Humans Enzyme Inhibitors Glucuronosyltransferase Hyperbilirubinemia chemistry.chemical_classification Sulfonamides Phenylurea Compounds Kinetics Pyrimidines Enzyme chemistry 030220 oncology & carcinogenesis Microsomes Liver Quinazolines medicine.drug |
| Zdroj: | Biochemical Pharmacology. 129:85-95 |
| ISSN: | 0006-2952 |
| Popis: | Kinase inhibitors (KIs) are a rapidly expanding class of drugs used primarily for the treatment of cancer. Data relating to the inhibition of UDP-glucuronosyltransferase (UGT) enzymes by KIs is sparse. However, lapatinib (LAP), pazopanib (PAZ), regorafenib (REG) and sorafenib (SOR) have been implicated in the development of hyperbilirubinemia in patients. This study aimed to characterise the role of UGT1A1 inhibition in hyperbilirubinemia and assess the broader potential of these drugs to perpetrate drug-drug interactions arising from UGT enzyme inhibition. Twelve recombinant human UGTs from subfamilies 1A and 2B were screened for inhibition by LAP, PAZ, REG and SOR. IC50 values for the inhibition of all UGT1A enzymes, except UGT1A3 and UGT1A4, by the four KIs were |
| Databáze: | OpenAIRE |
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