Hydroxylating Drugs: Why Bother?
Coming up on the 12th and 13th November are the next webinars in our popular “why bother?” series. Register using the options below to participate in the webinar on “Hydroxylating drugs: why bother?”. If you can’t make any of the times, contact us and we’ll send you a recording after the event.
Abstract: Late-stage oxidation of C-H bonds in drug compounds permits the diversification of structures to alter drug properties, without the need for de novo synthesis. The selective introduction of oxidized functionality, acting as hydrogen bond donors and acceptors in three-dimensional space, allows drug molecules to interact with hitherto unexploited sites within a target protein. Thus, pharmacological properties such as potency and selectivity can be influenced, as well as PK properties and physical attributes such as solubility and polarity.
In this webinar we explore case studies from the literature where hydroxylation has added value and resulted in lead compounds with improved properties. We’ll also examine projects in which PolyCYPs enzymes have been employed to achieve late-stage oxidation through a new process called PolarExplorer.
PolyCYPs® are a diverse set of cytochrome P450s cloned from actinomycete bacteria and expressed in E.coli, which allow scalable generation of multiple oxidized derivatives in parallel, including the synthesis of human CYP-derived metabolites. The wide range of organic molecules that these CYPs are able to oxidise enables their application for late-stage oxidation of different drug candidates, whilst simultaneously exploring the possibility of active metabolites.
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.
Abstract: 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.