Hypha Discovery: Metabolite synthesis, purification and identification experts
WHAT'S NEW - Q3 2022
Gut metabolites
Human faecal incubations
Our microbiology team have been busy developing a human faecal incubation system to produce gut metabolites. We've now used this to good effect in several client projects to make and identify both reduced and conjugated metabolites of their drugs.
Reduced metabolites of drugs
In the case studies illustrated in the link below, nizatadine and sulfasalazine were incubated in human faecal material derived from several mixed sex donors under oxygen depleted conditions. The reduced metabolites were easily detected by LC-MS.
Human faecal incubations can be scaled up to provide material for purification of multi mg amounts of metabolites prior to structure elucidation by cryoprobe NMR.
Phase II metabolites
Drug hunter phase II poster
Hypha were proud to support and contribute to this great resource from Drug Hunger on phase II drug metabolism, including case studies and a downloadable poster which summarises all the common and more unusual phase II mechanisms.
Amino acid drug conjugates
ISSX 2022 gave us the opportunity to present some interesting work we did with AstraZeneca. In addition to the main active human hydroxylated metabolites of the selective estrogen receptor degrader AZD9496, some unexpected conjugates formed by microbial biotransformation were produced and identified. These included glycine, alanine, serine and glutamine conjugates, and an oxidized N-acetylcysteine adduct.
Hypha works with many companies to synthesize, identify and scale-up all types of phase I and phase II metabolites. Our complementary expertise in chemical synthesis and scalable biotransformation solutions makes us the go to option to access metabolites up to kg scale.
Latest Resources - Blog and Poster
Bioisosteres that influence metabolism
Phenyl, carboxylic acid and amide groups are common functional groups that have well known issues around metabolism. In this blog Sam looks at how bioisosteres can alter metabolism of a drug using several case studies from the literature. As expected there are no "rules of thumb" for applying bioisosteres!
PolyCYPs: Biocatalytic Tools for the Optimisation of Drug Leads
We presented a poster on "PolyCYPs: Biocatalytic Tools for the Optimisation of Drug Leads" at a recent RSC meeting in London. The poster illustrates the benefits of using PolyCYPs, including identifying active metabolites, providing synthetic handles and broadening IP around drug leads.
About Hypha
Hypha are experts in the scalable synthesis, purification and structure elucidation of metabolites and impurities of drugs and agrochemicals. We work with pharma and agrochemical companies worldwide to fulfil our clients' needs to obtain metabolites for definitive MetID and for further biological testing. Applying a comprehensive portfolio of methods, including microbial and liver S9 / microsomal biotransformation methods, chemical synthesis, and recombinant enzymes, Hypha has the ability to produce gram amounts of synthetically challenging metabolites and oxidised derivatives of drugs. Combined with strong capabilities in purification chemistry and structural elucidation using state-of-the-art NMR spectroscopy, we are able to deliver an end-to-end service to clients.
