Glucuronide Metabolites, Why Bother?
We recently enjoyed hosting some popular and interactive webinars on “Glucuronide Metabolites, Why Bother?” If you missed these webinars and would like a link to a recording, please contact us.
The impact of conjugation of drugs by glucuronidation has attracted more interest in recent years. Evolution of drug design strategies away from single CYP mediated mechanisms towards more metabolically stable drugs has resulted in an increase in clearance by mechanisms such as glucuronidation. Metabolism of drugs by UDP-glucuronosyltransferases (UGTs) is the most important phase II route of metabolism resulting in the formation of 0-, N– and acyl glucuronides. In this webinar, we explored the need and routes to accessing different types of glucuronides, illustrated using case studies from the literature as well as recent examples from projects undertaken for Hypha’s clients.
One-Stop Metabolite Shop
If you missed our webinar on our One-stop Metabolite Shop: “New tools for metabolite synthesis: enhanced PolyCYPs+ kit and late-stage chemical glucuronidation“, but are interested in learning more, please contact us for a link to a recording.
In the webinar our CEO Dr Liam Evans shared Hypha’s new one-stop shop for metabolite synthesis, including our enhanced PolyCYPs®+ screening kits and a new late-stage chemical glucuronidation screen.
The chemical screen is suitable for synthesis of O-, N- and acyl glucuronides and features tailored deprotection strategies suitable for synthesis of acyl glucuronides and some unstable N-glucuronides. The chemical screen is complementary to our existing successful microbial and mammalian biotransformation routes for generating phase II conjugates.
The extended PolyCYPs®+ kits comprise 18 diverse CYP isoforms cloned from some of Hypha’s bacteria, as well as complimentary inclusion of two other phase 1 enzymes – human aldehyde oxidase (AOX1) and flavin monooxygenase 3 (FMO3), with other FMO isoforms to be incorporated as they become available.