Microbial biotransformation - an important tool for the study of drug metabolism
| Autor: | Jonathan Steele, Yong Liu, Liam Evans, Ronald de Vries, Richard Phipps, Cheri M Maciolek, Roy Helmy, Steven L. Colletti, Iain Martin, Gary E. Martin, Douglas C. Beshore, Natasa Pajkovic, Headley Williams, Rhys Salter, Yong Gong, James H. Small |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis Metabolite Toxicology 030226 pharmacology & pharmacy Biochemistry Chemical synthesis Hydroxylation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Biotransformation Humans Liver microsomes Pharmacology Safety studies Bacteria Drug discovery General Medicine 030104 developmental biology chemistry Pharmaceutical Preparations Metabolome Oxidation-Reduction Drug metabolism |
| Zdroj: | Xenobiotica; the fate of foreign compounds in biological systems. 49(8) |
| ISSN: | 1366-5928 |
| Popis: | Metabolite identification is an integral part of both preclinical and clinical drug discovery and development. Synthesis of drug metabolites is often required to support definitive identification, preclinical safety studies and clinical trials. Here we describe the use of microbial biotransformation as a tool to produce drug metabolites, complementing traditional chemical synthesis and other biosynthetic methods such as hepatocytes, liver microsomes and recombinant human drug metabolizing enzymes. A workflow is discussed whereby microbial strains are initially screened for their ability to form the putative metabolites of interest, followed by a scale-up to afford quantities sufficient to perform definitive identification and further studies. Examples of the microbial synthesis of several difficult-to-synthesize hydroxylated metabolites and three difficult-to-synthesize glucuronidated metabolites are described, and the use of microbial biotransformation in drug discovery and development is discussed. |
| Databáze: | OpenAIRE |
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