- Catalog No: MBE-0001
- Species: Human
- Source: ExpiSf9™ Cells
- Substrates: Bilirubin/Irinotecan/UK-157147/PF06409577 or others
- Overview:
- UGT1A1, standing for UDP-Glucuronosyltransferase 1A1, is a pivotal member of the extensive UDP-glucuronosyltransferase (UGT) superfamily, which plays a crucial role in the metabolism of various endogenous and exogenous compounds. Predominantly expressed in the liver, UGT1A1 exhibits its biological activity by catalyzing the conjugation of glucuronic acid, derived from UDP-glucuronic acid, to a wide range of substrates. This conjugation enhances the water solubility of the substrates, facilitating their excretion through bile or urine, thereby preventing toxic accumulation.
- Application in Drug Development:
- Drug Metabolism Prediction and Optimization:
- In the early stages of drug development, understanding the interaction between UGT1A1 and potential drug candidates is crucial. UGT1A1 is responsible for the metabolism of numerous drugs, including some chemotherapeutics like irinotecan. By assessing the drug’s affinity for UGT1A1 and predicting its metabolic pathway, researchers can optimize the drug’s structure to improve its pharmacokinetic properties, such as half-life and bioavailability.
- Toxicity Assessment and Mitigation:
- Drugs that undergo extensive metabolism by UGT1A1 can pose a risk of toxicity if their metabolites accumulate due to genetic variations or drug-drug interactions that affect UGT1A1 activity. Incorporating UGT1A1 screening into drug development allows for early identification of potential toxicity issues and the implementation of strategies to mitigate them, such as dose adjustments or the development of alternative metabolic pathways.
- High-Throughput Screening Platforms:
- To accelerate the drug discovery process, researchers utilize high-throughput screening platforms that enable the rapid assessment of thousands of compounds for their interaction with UGT1A1. These platforms incorporate advanced technologies, such as fluorescence-based assays and mass spectrometry, to identify potential drug candidates with favorable metabolic profiles.
- In Vitro and In Vivo Models:
- The development of in vitro cell lines and in vivo animal models that recapitulate human UGT1A1 activity has significantly advanced our understanding of drug-UGT1A1 interactions. These models provide valuable insights into the metabolic fate of drugs and enable the prediction of human pharmacokinetic profiles, thereby reducing the risk of failure in clinical trials.
- 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.
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