What We Do

Metabolite Synthesis

Synthesis of Metabolites of Drugs and Agrochemicals

Hypha are go-to experts in provision of phase I and phase II metabolites to pharma and agrochemical companies. We have worked with over 110 companies and organisations worldwide to provide metabolites for discovery and development stage projects.

We provide metabolites to clients for a variety of applications:

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:

Hyphas one stop metabolite shop gif

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.

Stable-labelled and radiolabelled metabolites

We are able to make, [13C], [14C], [2H], [3H] and [15N]-labelled metabolites to support regulatory, development or research projects in the pharma and crop protection industries. Hypha first establishes an optimised process using unlabelled parent substrates, before scale-up to produce the stable-labelled or radiolabelled metabolites. We work with our partner Selcia to produce and purify the radiolabelled material, the process for which is transferred from Hypha’s facility by our scientists to Selcia’s state-of-the-art radiochemistry labs, also located in the UK.
Read more

Metabolites of agrochemicals

In addition to metabolites of drugs, Hypha’s biotransformation platform is also effective for the production of animal and plant metabolites of agrochemicals, including glycosides. Our processes have been specially adapted to accept and metabolise pesticides which typically have poor aqueous solubility.

Key features

Phase 1 metabolites produced from both CYP and non-CYP mediated pathways, including via aldehyde oxidase and FMOs

Production of Phase 2 conjugates, including N- , O- &
acyl glucuronide and sulfated metabolites

Multiple metabolites can be captured in a single screen

Applicable to broad structural types and complex molecules

Solutions for synthetically challenging metabolites

Provides a tool for MetID and for accessing larger quantities of metabolites for further biological characterisation to satisfy regulatory requirements

Reproducible and scalable process to gram quantities

Formulation know-how for poorly-soluble compounds

Tailored project design and stage-gated payment structure

Simple fee for-service basis, i.e. there are no downstream terms or royalties

Resources

Explore our library of resources comprising brochures, case studies, posters and publications about the work we do.

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.

Test tubes with dripper
251A3171-DE01-48EB-AA27-BD82BC5AC10DCreated with sketchtool.

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

Ready to begin? Our scientists are available to talk through your requirements

Contact Us

Don't forget to subscribe to our newsletter and blog!

Newsletter Signup
Which do you wish to signup for?