What We Do
Synthesis, identification and purification experts
Your trusted partner in pharmaceutical and agrochemical R&D
Hypha Discovery is a specialist CRO supporting pharmaceutical and agrochemical companies worldwide. We are experts in:
MetID, synthesis and purification of phase I and II metabolites at mg/g/kg scale using late-stage biological and chemical methods
Access to gut metabolites using pooled human faecal incubations, and drug stability in the gut environment
Structure elucidation using cryoprobe NMR spectroscopy
Stability testing of metabolites
Purification of metabolites from biological matrices such as plasma, urine etc.
Isolation and identification of impurities from manufacturing batches
Production of late-stage oxidised derivatives of lead compounds
Production, purification and structure elucidation of natural products, including strain improvement
NMR Spectroscopy and Structure Elucidation
NMR Spectroscopy and Structure Elucidation
• Quantitative NMR
• Interpretation and documentation of spectra to publication standard
Our Metabolite Expertise
Hypha’s One-Stop Metabolite Hub
Hypha Discovery offer a comprehensive suite of services as part of our one-stop metabolite hub.
Our LC-MS/MS based MetID services enables identification of metabolic soft spots in early-stage compounds through to conducting detailed MetID biotransformation studies of lead candidates.
Hypha’s One Stop Metabolite Shop delivers even the most challenging-to-synthesise metabolites, making it the go-to solution for all your metabolite requirements. We use chemical synthesis, microbial biotransformation, recombinant enzymes such as PolyCYPs, PolyUGTs, and mammalian liver and other tissue fractions. We are also experts in purification of metabolites from biological matrices, and structure elucidation by cryoprobe NMR.
Our strategy allows production of Phase I, Phase II and mixed phase metabolites from microgram scale for definitive MetID, and up to multi mg / gram scale for further biological evaluation and provision of certified bioanalytical standards.
We also provide a service to access and identify gut metabolites using human and rat faecal incubations performed under anaerobic conditions.
Chemical Synthesis
Late-stage chemical glucuronidation
Mammalian biotransformation
Panels of liver S9s / microsomes / hepatocytes
Microbial biotransformation
Proven panels of bacteria and fungi
Gut metabolism
Anaerobic human faecal incubations
Recombinant enzymes
PolyCYPs, PolyUGTs, hrCYPs, AOX, FMOs
Purification & structure elucidation
COAs, acquisition / interpretation of NMR data
Our Products
Hypha has developed several recombinant enzyme products that can be used for making metabolites, either for use in your own lab, or by contracting Hypha to do the testing.
To access Phase I drug metabolites, our key enzymes include a set of proprietary diverse microbial CYPs called PolyCYPs®, as well as human recombinant aldehyde oxidase (AOX1) and all five human isoforms of flavin-containing monooxygenase (FMOs). Each enzyme is cloned into E.coli and validated against a panel of relevant drug substrates to demonstrate utility. A set of 18 PolyCYPs enzymes, AOX1 and FMO3 are available in the PolyCYPs+ screening kit.
PolyCYPs can also be used as an effective tool to expand the medicinal chemistry toolbox to access late-stage oxidised derivatives of drugs. Hydroxylation has been identified by scientists as “a key tactic to consider as part of a late-stage functionalization strategy” (Bostrom et al., 2018). PolyCYPs can address this need by providing a fast and easy way to hydroxylate aliphatic or aromatic moieties at multiple sites in parallel.
For accessing Phase II metabolites, Hypha’s PolyUGTs kits provide an easy-to-use solution for synthesis of acyl, O– and some N-glucuronides.
PolyUGT enzymes are cloned from a subset of Hypha’s bacterial strains adept at making glucuronides. They are expressed in E.coli, purified and provided in a kit form together with UDPGA co-factor.
Scale-up vials are available for all enzymes, and for accessing larger amounts of metabolites using whole cell biotransformation, Hypha can undertake the work.
PolyCYPs and PolyUGTs kits
Our kits are simple to use. They contain all co-factors needed to screen a drug substrate, as well as a control compound and formulant for poorly water-soluble test compounds.
In addition to the enzymes supplied in PolyCYPs+ and PolyUGTs kits, Hypha offers a service to screen compounds against any of our recombinant enzymes, including all five human FMO isoforms.
All recombinant enzymes are fully scalable to provide larger quantities of metabolites. Scale-up vials of each isoform are available, as well as the ability to scale-up large quantities of metabolites at Hypha as a service offering. We can also undertake purification and structure elucidation of metabolites by NMR spectroscopy.
Publications
Read about our publications in the fields of metabolite synthesis, biotransformation and natural products chemistry
Brochures
Access brochures on drug metabolite synthesis, Hypha’s one-stop metabolite shop and the PolyCYPs platform
Ready to begin? Our scientists are available to talk through your requirements
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.