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Hypha Discovery Ltd.

Uxbridge, GB

Hypha Discovery is a microbial technology company helping partners in pharmaceutical and agrochemical R&D succeed through the discovery and production of microbial and mammalian metabolites. We are experts in the scalable production of DMPK metabolites, including glucuronides and aliphatic hydroxyls, and generation of polar analogues, and are also a leading provider of unique natural product screening libraries and associated services.

Why work with us?

Our track record in natural products. Our client base of pharmaceutical and agrochemical multinationals and SMEs, is testament to our expertise in fermentation, purification, identification and biotransformation of small molecules.

Cost effective, flexible service. Clients may outsource entire programs or choose to work with us on a modular basis. We can also troubleshoot and rework existing processes and provide a full handover to clients.

Our... Show more »

Hypha Discovery is a microbial technology company helping partners in pharmaceutical and agrochemical R&D succeed through the discovery and production of microbial and mammalian metabolites. We are experts in the scalable production of DMPK metabolites, including glucuronides and aliphatic hydroxyls, and generation of polar analogues, and are also a leading provider of unique natural product screening libraries and associated services.

Why work with us?

Our track record in natural products. Our client base of pharmaceutical and agrochemical multinationals and SMEs, is testament to our expertise in fermentation, purification, identification and biotransformation of small molecules.

Cost effective, flexible service. Clients may outsource entire programs or choose to work with us on a modular basis. We can also troubleshoot and rework existing processes and provide a full handover to clients.

Our processes are scalable. Target molecules can be produced for further work from mg amounts to assess bioactivity, up to g scale and beyond for semi-synthetic modification.

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Metabolite Generation
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Drug and Environmental Fate (eFate) Metabolites

We mimic mammalian phase I and phase II metabolism using our talented microorganism panels to produce metabolites for unambiguous identification, use as quantitation standards or larger amounts for DMPK/ADME/TOX studies. Metabolites arising from a variety of processes are... Show more »

Drug and Environmental Fate (eFate) Metabolites

We mimic mammalian phase I and phase II metabolism using our talented microorganism panels to produce metabolites for unambiguous identification, use as quantitation standards or larger amounts for DMPK/ADME/TOX studies. Metabolites arising from a variety of processes are accessible, including both CYP and non-CYP derived mechanisms. We can also produce phase II conjugates such as N-, O- and acyl glucuronides.

Microbial biotransformation will produce most mammalian metabolites as it is well-established that microbial organisms mimic mammalian metabolism of small molecules (1, 2) due to evolutionarily-related enzyme systems. We have been able to demonstrate that our biotransformation panel are able to undertake these common reactions, amongst many others.

References

1) Smith & Rosazza, Arch. Biochem Biophys. (1974) 161: 551-558.
2) Azerad, R., Adv Biochem Eng Biotechnol (1999) 63, 169.

Key features:

  • Phase I metabolites produced from both CYP and non-CYP mediated pathways
  • Production of Phase II conjugates, including N-,O- & acyl glucuronide metabolites
  • Multiple metabolites can be captured in a single screen
  • Scalable and reproducible process
  • Target molecules can be produced at mg/g quantities for pharmacology/toxicology
  • Applicable to broad structural types and complex molecules, including natural products and synthetic compounds
  • Formulation know-how for poorly-soluble compounds
  • Provides a solution for synthetically challenging metabolites when synthesis is not possible or too costly / time-consuming
  • Provides a tool for MetID and producing metabolites at greater scale
  • Metabolites are produced on a simple fee-for-service basis, i.e. there are no downstream terms or royalties
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Natural Product Isolation and Purification
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There is renewed interest in natural products as a source of chemical entities, either through discovery of new scaffolds or re-evaluating previously discovered bioactive chemicals.

Hypha has expertise spanning microbial strain handling, fermentation and improvement, through to the purification and structure elucidation of the... Show more »

There is renewed interest in natural products as a source of chemical entities, either through discovery of new scaffolds or re-evaluating previously discovered bioactive chemicals.

Hypha has expertise spanning microbial strain handling, fermentation and improvement, through to the purification and structure elucidation of the target compounds, as well as bioactivity testing. We are able to work flexibly with clients to provide any aspect required.

Examples of projects we can undertake include production of natural product scaffolds for semi-synthetic modification, production and purification of ADC-payloads and purification of bioactive molecules from mixtures. We are able to supply milligram to gram amounts of compounds and have access to multi-thousand litre scale reactors via an alliance with a fermentation provider.

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Cytotoxicity Assays
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We are able to test samples against a panel of cell lines using methods based on those employed by the US National Cancer Institute (NCI), which enables the assessment of mode of effect, i.e., cytotoxicity, anti-proliferation and cell-cycle arrest, based upon the inhibition curve observed.

We are able to test samples against a panel of cell lines using methods based on those employed by the US National Cancer Institute (NCI), which enables the assessment of mode of effect, i.e., cytotoxicity, anti-proliferation and cell-cycle arrest, based upon the inhibition curve observed.

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Natural Product Libraries
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The structural diversity and biological efficacy of natural products makes them attractive for inclusion in modular screening campaigns, both as a source of novel scaffolds and as a tool to probe biological targets.

Hypha’s MycoDiverseTM libraries of low molecular weight natural product samples derive from unusual fungi... Show more »

The structural diversity and biological efficacy of natural products makes them attractive for inclusion in modular screening campaigns, both as a source of novel scaffolds and as a tool to probe biological targets.

Hypha’s MycoDiverseTM libraries of low molecular weight natural product samples derive from unusual fungi including the mushroom producing basidiomycetes. We have designed novel stimulatory mechanisms to elicit metabolite production in these fungi, resulting in extracts and fractions rich in bioactive secondary metabolites. Application of this unique fermentation approach to these under-explored microbes results in nearly 50% of the bioactive compounds characterised being novel in structure.

Our commercial terms present a low barrier to entry and a reduced-risk progression to the production and structure elucidation of the most promising hit compounds, as well as the guarantee to exclusive access to hit compounds giving strong IP protection for our clients.

Fundamental to the design of these unique screening resources is assay compatibility. Fermentations broths are processed to generate fractions of grouped polarities that are free of proteinases and polysaccharides and proven to be compatible with a variety of screening formats.

The clogP values of bioactive compounds structurally characterised from the library range from -1 to +9. The more polar compounds generally originate from the aqueous broths but the picture is complex, with many compounds of low to medium polarity present in the biomass extracts while some molecules with high clogP values are found in the most non-polar broth fractions.

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Natural Product Discovery by Microbial Fermentation
Price on request

There is renewed interest in natural products as a source of chemical entities, either through discovery of new scaffolds or re-evaluating previously discovered bioactive chemicals.

Hypha has expertise spanning microbial strain handling, fermentation and improvement, through to the purification and structure elucidation of the... Show more »

There is renewed interest in natural products as a source of chemical entities, either through discovery of new scaffolds or re-evaluating previously discovered bioactive chemicals.

Hypha has expertise spanning microbial strain handling, fermentation and improvement, through to the purification and structure elucidation of the target compounds, as well as bioactivity testing. We are able to work flexibly with clients to provide any aspect required.

Examples of projects we can undertake include production of natural product scaffolds for semi-synthetic modification, production and purification of ADC-payloads and purification of bioactive molecules from mixtures. We are able to supply milligram to gram amounts of compounds and have access to multi-thousand litre scale reactors via an alliance with a fermentation provider.

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Natural Product Screening
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Hit to Lead and Lead Optimization
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Our microbial panels not only mimic mammalian metabolism but have the added benefit of also producing other derivatives that might not have been considered or accessible using synthetic routes. The process is complementary to medicinal chemistry and can be exploited to diversify hit or lead compounds by generating oxidised... Show more »

Our microbial panels not only mimic mammalian metabolism but have the added benefit of also producing other derivatives that might not have been considered or accessible using synthetic routes. The process is complementary to medicinal chemistry and can be exploited to diversify hit or lead compounds by generating oxidised molecules that may have greater activity, better selectivity or an improved availability profile than the parent molecule. It can also be used to help widen and protect IP and inform SAR. The technology can be applied at the lead optimisation stage or on compounds at earlier hit or hit-to-lead stages.

Solve Excessive Lipophilicity

If you are looking to create more polar metabolites to improve solubility, we can apply our proven lipophilic rescue service to achieve improvement in LLE/LipE. The technology has the added benefit that multiple analogues can be produced in a single process. Selected derivatives can then be optimised and the production scaled-up.

Create Handles for Synthesis

Our process can create handles for further structural changes such as fluorination used for metabolism blocking or PET ligand formation.

Key features of our lead diversification service:

  • Flexible options – the process can be tailored to client needs
  • Provides a unique method for generating metabolites that are challenging to create synthetically
  • Scalable and reproducible process
  • Multiple metabolites can be captured in a single screen
  • Applicable to broad structural types and complex molecules, including natural products
  • Target molecules are produced at mg/g scale
  • Defined timelines and costs
  • Metabolites are produced on a simple fee-for-service basis, i.e. there are no downstream terms
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Biology
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Omics
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Metabolomics
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Pharmacology & Toxicology
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Toxicology
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Drug Discovery & Development
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Drug Discovery
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Lead Identification and Validation
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Compound Libraries
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Natural Products
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