- Catalog No: MBE-0005
- Species: Human
- Source: ExpiSf9™ Cells
- Substrates: 7- hydroxy-4-trifluoromethylcoumarin/NSAIDs/cetaminophen / propranolol/aspirin or Others
- Overview:
- Overview of UGT1A6 Enzyme:
UGT1A6, formally known as UDP-Glucuronosyltransferase 1A6, is a member of the UGT superfamily, which comprises a diverse group of enzymes essential for the phase II metabolism of numerous endogenous and exogenous compounds. Encoded by the UGT1A6 gene located on chromosome 2q37, UGT1A6 is a critical drug-metabolizing enzyme that catalyzes the glucuronidation of various substrates, including drugs, hormones, and toxicants. This process enhances the water solubility and facilitates the elimination of these compounds from the body.
Key Features of UGT1A6:
Tissue Distribution: UGT1A6 is predominantly expressed in the liver, where it plays a pivotal role in drug metabolism and detoxification. It is also found in other tissues such as the biliary tract, colon, stomach, and brain, contributing to the overall glucuronidation capacity of the body.
Substrate Specificity: UGT1A6 exhibits a broad substrate spectrum, capable of glucuronidating various compounds, including drugs like acetaminophen (paracetamol), propranolol, and aspirin, as well as endogenous compounds like serotonin and certain toxicants.
Genetic Polymorphisms: Like other UGT enzymes, UGT1A6 displays genetic variability, with several single nucleotide polymorphisms (SNPs) identified. These polymorphisms can significantly impact the catalytic activity and substrate specificity of UGT1A6, leading to interindividual differences in drug response and
- Application in Drug Development:
- Drug Metabolism Prediction and Optimization:
- UGT1A6’s critical role in drug metabolism makes it an essential target for predicting the metabolic fate of new drug candidates. By studying the interaction between UGT1A6 and potential drug substrates, researchers can gain insights into the drug’s pharmacokinetics, including its absorption, distribution, metabolism, and excretion (ADME) properties.
- Toxicity Assessment and Mitigation:
- As UGT1A6 is involved in the detoxification of various toxicants, its activity can influence the toxicity profile of drugs. By assessing the impact of UGT1A6 on drug metabolism, researchers can identify potential toxicity concerns early in the drug development process and adjust the drug’s structure or dosing regimen accordingly.
- High-Throughput Screening Platforms:
- UGT1A6’s involvement in the metabolism of multiple drugs makes it a potential contributor to drug-drug interactions. By studying the interactions between UGT1A6 and other drugs, researchers can identify potential inhibitors or inducers of UGT1A6 activity and develop strategies to mitigate their effects.
- In Vitro and In Vivo Models:
- The development of in vitro and in vivo models that mimic human UGT1A6 activity has facilitated drug development efforts. These models enable researchers to study drug-UGT1A6 interactions in a controlled environment, predict human pharmacokinetic profiles, and assess the impact of genetic variations on drug metabolism. The use of recombinant UGT1A6 enzymes and genetically engineered cell lines has significantly advanced our understanding of UGT1A6’s role in drug metabolism.
- Appearance: Lyophilized powder.
- Endotoxin Level: <1.0 EU/μg, determined by LAL method.
- Purity: Greater than 90% as determined by reducing SDS-PAGE.
- Storage & Stability: Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer. It is recommended to freeze aliquots at -20°C or -80°C for extended storage.
