- Catalog No: MBE-0008
- Species: Human
- Source: ExpiSf9™ Cells
- Substrates: N-hydroxy aromatic amines, anthraquinones/estrogens/sterols/diazepam/coumarins/mycophenolic acid or others
- Overview:
- ntroduction to UGT1A9 Enzyme
UGT1A9, encoded by the UGT1A9 gene located on chromosome 2q37, belongs to the UGT1A subfamily of UDP-glucuronosyltransferases (UGTs). These enzymes play a crucial role in phase II metabolism by catalyzing the transfer of glucuronic acid from uridine diphosphate glucuronic acid (UDPGA) to various lipophilic substrates, including xenobiotics, endogenous compounds, and drugs. This glucuronidation process enhances the water solubility and excretion of these compounds, thus facilitating their elimination from the body.
Key Characteristics and Distribution
Composed of 530 amino acids, UGT1A9 is predominantly expressed in the liver and kidneys.
It is an essential enzyme involved in the glucuronidation of a wide range of substrates, including toxicants (e.g., phenolic compounds, N-hydroxy aromatic amines, anthraquinones), endogenous substances (such as estrogens and sterols), and various drugs (e.g., diazepam, coumarins, mycophenolic acid).
- Application in Drug Development:
- Drug Metabolism Prediction and Optimization:
- UGT1A9 plays a critical role in the metabolism and elimination of numerous therapeutic drugs. Its involvement in the glucuronidation of these compounds directly impacts their pharmacokinetics, pharmacodynamics, and ultimately, their therapeutic efficacy and safety profiles.
For instance, UGT1A9 metabolizes mycophenolic acid, a widely used immunosuppressant in renal transplant patients. Variations in UGT1A9 activity can significantly alter mycophenolic acid pharmacokinetics, leading to variations in drug exposure and potentially affecting clinical outcomes.
- UGT1A9 plays a critical role in the metabolism and elimination of numerous therapeutic drugs. Its involvement in the glucuronidation of these compounds directly impacts their pharmacokinetics, pharmacodynamics, and ultimately, their therapeutic efficacy and safety profiles.
- Toxicity Assessment and Mitigation:
- High-Throughput Screening Platforms:
- In the drug discovery pipeline, knowledge of UGT1A9’s substrate specificity and its role in drug metabolism can guide the design of safer and more effective drugs.
By incorporating UGT1A9’s metabolic pathways into early-stage drug screening, researchers can identify potential drug-drug interactions and optimize drug candidates for improved pharmacokinetic profiles.
- In the drug discovery pipeline, knowledge of UGT1A9’s substrate specificity and its role in drug metabolism can guide the design of safer and more effective drugs.
- In Vitro and In Vivo Models:
- 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.
