UGT Investigation

Creative Biolabs has made a long-term commitment to discovering and developing future drugs for solving worldwide unmet health issues. Currently, we offer integrated service of UGT investigation by our well-established assay platform.

Drug-drug interaction (DDI) is a major concern when multiple drugs are co-administrated and interfere the metabolism of one another. In effort to minimize DDI liability, a comprehensive understanding of drug metabolism pathway and interference potency on key enzymes is absolutely crucial. In general, enzymes participating in catalyzing chemical conversions during most drug metabolizing process can be characterized as Phase I enzymes (mainly CYP) and Phase II enzymes (such as glutathione-S-transferases and UGT). Particularly, uridine glucuronyl transferase (UGT) represents one predominant enzyme in Phase II, which is involved in the metabolism pathways of 10% of the top 200 prescribed drugs. Additionally, UGT1A1, one UGT isoform, also plays a part in the glucuronidation of many endogenous products, such as bilirubin, estrogens, and flavonoids. Hence, inhibitory or inducing potentials of certain components might not only cause DDI side effects but also impair normal internal metabolism. Currently, UGT profiles are strongly recommended by regulatory authorities as part of in vitro DDI packages for IND submission.

Figure 1. The Proportion of Drugs Metabolized by the Major Phase I and Phase II Enzymes.

Creative Biolabs presents multiple UGT-focused assays to provide our clients detailed information for subsequent optimizing and decision-making.

UGT Inhibition Test

The basic principle and test method are similar to CYP inhibition test. Our featured UGT inhibition test can satisfy following requirements:

• Six isoforms available to be evaluated, including UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, and UGT2B7.
• Different expression systems of choice: recombinant enzymes, pooled human liver microsomes, HepaRG™ cell line or cryopreserved hepatocytes.
• Highly-specific probe substrates and positive control inhibitors.
• LC-MS/MS technology used to monitor the formation of substrate metabolites.
• Customized concentration ranges.
• Direct IC₅₀ value to estimate UGT inhibiting property of test compounds. K_i service is also available to validate inhibition potency and type.

UGT Induction Test

Similar to CYP, UGT is also inducible by chemical substances. Given the essential status of UGT in glucuronidation of many conjugative drugs, Creative Biolabs offers induction test of all 6 UGT isoforms. Both mRNA alterations and enzymatic activities will be measured using pooled human primary hepatocytes. Full submission quality report with precise IC₅₀ value will be delivered to our customers in a short time.

UGT-Reaction Phenotyping Assay

This assay can provide direct insight into whether UGT isoform-specific catalyzing exists in the metabolism pathway of your component. By incubating test compound with recombinant UGT isoforms and alamethicin, UDPGA (essential reaction reagents) at 37°C, and monitoring the compound clearance rate, we can infer the UGT responsible for metabolizing and predict DDI risks.

In addition to UGT and CYP investigation, Creative Biolabs also provides a range of other metabolism enzymes available for testing. With high-quality assessing data and professional interpretation and advice, Creative Biolabs is always ready to assist our customers in paving the way for cutting-edge drug development.

For more detailed information, please feel free to contact us or directly sent us an inquiry.

For Research Use Only.