- Catalog No: MBE-0004
- Species: Human
- Source: ExpiSf9™ Cells
- Substrates: Trifluoperazine/Bilirubin or others
- Overview:
- UGT1A4, standing for UDP Glucuronosyltransferase 1 Family, Polypeptide A4, is a crucial member of the UGT (Uridine Diphosphate Glucuronosyltransferase) superfamily, a diverse group of enzymes responsible for the conjugation of glucuronic acid to various substrates, including drugs, hormones, and other xenobiotics. Located primarily in the endoplasmic reticulum, UGT1A4 is a membrane-bound enzyme that catalyzes the transfer of glucuronic acid from UDP-glucuronic acid (UDPGA) to acceptor molecules, resulting in the formation of water-soluble glucuronidated metabolites that are easily excreted from the body.
Key Features of UGT1A4:
Tissue Distribution: UGT1A4 is expressed abundantly in the liver, bile duct, colon, small intestine, and pancreas, among other tissues. Its broad distribution underscores its significance in drug metabolism and detoxification across various organ systems.
Substrate Specificity: UGT1A4 exhibits a broad substrate spectrum, metabolizing a wide range of drugs and endogenous compounds. Notably, it is the primary metabolic enzyme for several antiepileptic drugs, including lamotrigine.
Genetic Polymorphisms: Like other UGT enzymes, UGT1A4 displays genetic variability, with certain polymorphisms known to impact its catalytic activity and substrate affinity. These genetic variations can influence interindividual differences in drug response and metabolism.
- Application in Drug Development:
- Drug Metabolism Prediction and Optimization:
- UGT1A4’s critical role in drug metabolism makes it a valuable target for predicting the metabolic fate of potential drug candidates. Understanding its substrate specificity and kinetic properties can help researchers optimize the pharmacokinetic profiles of new drugs and anticipate potential drug-drug interactions.
- Toxicity Assessment and Mitigation:
- The involvement of UGT1A4 in the metabolism of various compounds, including potential toxicants, underscores its importance in toxicity assessment. By evaluating the impact of UGT1A4 on drug metabolism and elimination, researchers can identify potential safety concerns early in the drug development process.
- High-Throughput Screening Platforms:
- As UGT1A4 is involved in the metabolism of multiple drugs, it can be a significant contributor to drug-drug interactions. Studying the interactions between UGT1A4 and other drugs can help researchers identify potential inhibitors or inducers of UGT1A4 activity, enabling the development of safer and more effective drug combination therapies.
- In Vitro and In Vivo Models:
- The development of in vitro and in vivo models that mimic human UGT1A4 activity has significantly advanced drug development efforts. These models enable researchers to study drug-UGT1A4 interactions in a controlled environment, predict human pharmacokinetic profiles, and assess the impact of genetic variations on 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.
