mail@hyphadiscovery.com Search What We Do Products Our Metabolite Expertise Why Choose Us About Us Resources News & Blog Events Contact Us Case Studies Case Studies and Client Projects Latest Case Studies Metabolite Production using PolyCYPs PolyCYPs were used effectively to produce a hydroxylated metabolite of OSA821, a lead compound in the Open Source Antibiotics (OSA) diarylimidazole series. READ MORE Scale-up of human metabolites from mixed metabolism of epacadostat Formation and scale-up of human metabolites formed through mixed metabolic pathways is possible using Hypha’s microbial biocatalysis system. In vivo human metabolism of Incyte’s IND epacadostat (EPA) forms 3 major circulating metabolites, from both primary and secondary pathways. Glucuronidation of EPA forms M9, the dominant metabolic pathway, in conjunction with formation of an amidine M11 and an N-dealkylated metabolite, M12. READ MORE Supply of stable-labelled and radiolabelled metabolites and microbial natural products Hypha’s microbial biocatalysis process is effective at generating metabolites at up to gram scale. Through Hypha and Selcia’s partnership, [13C], [14C], [2H], [3H] and [15N]-labelled metabolites can be accessed to support regulatory, development or research projects in the pharma and crop protection industries. Hypha establishes optimized processes using unlabelled or stable labelled parent substrates, which can then be transferred to Selcia’s state-of-the-art radiochemistry labs for the production of radiolabelled metabolites. READ MORE Rapid scale-up and supply of a hydroxylated metabolite In this case study at least 2 mg of a monohydroxylated metabolite (M4), originally observed in rat liver microsomes, was required by a US pharma company. Using PolyCYPs, the target metabolite was supplied to the client together with a Certificate of Analysis within 22 days from receipt of order, exemplifying the short timelines achievable using PolyCYPs to access CYP-derived metabolites. READ MORE Sulfated Drug Metabolites Phase 2 conjugated metabolites such as sulfates can be screened for and scaled-up using a variety of methods including microbial biotransformation, mammalian biotransformation and chemical synthesis. The chemical sulfation screens work well for both aliphatic and aromatic alcohols. Metabolites can be supplied at microgram to multi mg scale, and at gram scale via the microbial and chemical synthesis routes. READ MORE Scale-up of PolyCYPs Reactions Once a target metabolite or oxidised derivative has been synthesised by one or more PolyCYPs enzymes in the screening kit, a scale-up reaction with the best performing isoform is performed in order to access mg amounts of material for MetID and biological testing. The quickest and most cost-effective route for generating low mg amount of product is through the use of scale-up vials. Higher amounts of product can be generated using either a recombinant cell paste or through fermentation of a recombinant streptomyces clone expressing the isoform responsible for the biotransformation. READ MORE Application of PolyCYPs for Metabolite Identification from Radiolabelled Mass Balance Studies Hypha’s PolyCYPs kits are in routine use by pharma and agchem companies for producing human and other mammalian metabolites. One application involves use of PolyCYPs for creating radiolabelled metabolites for direct comparison with the radio profiles from mass balance and distribution study samples, necessary for regulatory filing. PolyCYPs provides a clean route for scalable access to more of the CYP-derived metabolites observed in these matrices, for definitive MetID and any tox studies deemed necessary. This is especially useful where low concentrations or unstable metabolites in the mass balance sample make structural identification difficult. READ MORE Off-target Activity of Drug Metabolites Many metabolites of drugs are wholly or partly responsible for both on-target or off-target in vivo activity. Metabolites of some drugs may initially be considered pharmacologically inactive, yet further investigation yields surprising alternative effects via different mechanisms. Off-target effects might synergize with the on-target effects or have other beneficial outcomes which could enhance or broaden the indication of the drug. READ MORE Regio-selective Formation of N-oxide Metabolites Formation of N-oxide metabolites is one of the major pathways for metabolism of tertiary nitrogen-containing drugs. Some N-oxide metabolites have similar or greater pharmacological activity to the parent drug and thus require exposure assessment. They can also be unstable and can revert to the parent drug. 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