Metabolites arising from a variety of pathways are accessible, including both CYP and non-CYP derived phase I mechanisms and phase II conjugates including all types of glucuronides.
We are typically asked to produce the following metabolite types:
- Oxidised metabolites
- Acyl glucuronides
- N-carbamoyl glucuronides
- Sulfated metabolites
- GSH conjugates
- Mixed pathway or multi-step metabolites, e.g. hydroxylated/glucuronidated metabolites
- Stable-labelled and radiolabelled metabolites
Our “One-stop Metabolite Shop” concept comprises a comprehensive suite of technologies to enable scalable synthesis of even the most difficult-to-synthesise metabolites. Human and other mammalian phase I and phase II metabolism of drugs and agrochemicals can be synthesised using a variety of methods to maximise the chances of success, including chemical synthesis, mammalian biotransformation (S9s / microsomes of liver and other tissues), microbial biotransformation, recombinant enzymes such as PolyCYPs, as well as the purification of metabolites from biological matrices. Hypha scientists are also experts in structural elucidation and NMR spectroscopy.
PolyCYPs+ kits contain 20 enzymes effective for producing a wide range of phase 1 metabolites. As well as 18 PolyCYPs enzymes, the kit also contains human aldehyde oxidase (AOX1) and the main human hepatic flavin-containing monooxygenase (FMO3), with other human FMO isoforms also available from Hypha. PolyCYPs® enzymes have been mined from talented actinomycete bacteria in Hypha’s biotransformation panel, providing a wide diversity of CYPs that oxidize a variety of drug compounds. Both human and other mammalian CYP-mediated metabolites can be produced.
We offer a comprehensive suite of techniques for provision of even the most difficult-to-synthesize metabolites, comprising chemical synthesis, recombinant enzymes, microbial biotransformation, mammalian liver fractions, in addition to the purification of metabolites from biological matrices. Hypha scientists are also experts in structural elucidation via NMR spectroscopy.
In Chapter 4 of the book on “Identification and quantification of drugs, metabolites, drug metabolizing enzymes and transporters”, Hypha authors summarise the different methods employed for producing metabolites of drugs, illustrated with representative examples from the literature and work undertaken at Hypha. The chapter also includes a discussion and examples of the use of NMR spectroscopy for structure elucidation of metabolites.
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Hypha has exceeded our expectations and is now a ‘go to’ lab for biosynthesis/synthesis/purification. Hypha’s team was a pleasure to work with and our complicated projects were handled with expertise and professionalism. Their excellent scientific communication and project data were extremely comprehensive and we received updates throughout the process. We will definitely be Hypha Discovery clients for life
Director of DMPKHead of Toxicology
DMPX, US Pharma Company
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Hypha Discovery is a UK-based CRO supporting pharmaceutical and agrochemical companies worldwide through the production of metabolites and new derivatives of drugs and agrochemicals in discovery and development.