Hypha Discovery: metabolite synthesis, purification and identification experts
WHAT'S NEW - Q1 2022
API Degradation Products
Hypha have put together a set of late stage chemical oxidation conditions, resulting in a toolbox for the synthesis and identification of degradation products. Our expertise in biotransformation and micro-purification, widens the suite of techniques to make and identify API degradation products and impurities.
Features
Purification from shelf life study samples, and structure elucidation by cryoprobe NMR, e.g. on ~100 micrograms.
Panel of late stage chemical oxidation conditions to synthesise mg-g amounts.
Complemented by microbial and enzymatic biotransformation.
Purification of Drug Impurities
Hypha purified and identified two sucralose conjugates of fluoxetine, formed during a study where the drug had been stored at 50oC for 2 months. Simulation of the reaction at 50oC for 7 days permitted purification and identification of two sucralose conjugates. Subtle differences in the NMR spectra revealed the presence of stereoisomers resulting from the reaction of sucralose with racemic fluoxetine.
Metabolism of Steroids
Hypha have worked on a number of interesting projects where metabolites of steroid scaffolds were needed. Our molecular biologists and chemists have devised various ways to access and purify these, including through the application of PolyCYPs enzymes.
Targeted CYP active site residue engineering can cause a change in the position of hydroxylation
PolyCYP 612 was shown to hydroxylate a steroid compound at the C7 and C14 positions with 100% conversion. Hypha's recombinant technology team generated several mutants including PolyCYP 646 which specifically hydroxylates the same steroid, predominantly at the C7 position.
Illustrated using generic steroid ring system (actual parent structure not shown)
Products of risperidone produced in Hypha’s chemical oxidation screen. The two major reported degradation products are shaded - an N-oxide and 9-hydroxy risperidone (also known as paliperidone, the primary active metabolite)
Metabolite Tales Blogs
We bring you 3 new interesting blog articles since our last newsletter:
Today’s Medicinal Chemist – a checklist for Candidate selection
Consultant Steve Djuric shares his thoughts and ideas on the challenges today's medicinal chemists face in selecting drug candidates. Steve debates hot topics around PK demands, such as permeability, CYP / AO metabolism, and the impact of AI.
Guest blogger and Consultant Guy Webber discusses what elements we need to worry about to help mitigate against failures in the drug discovery and development process, and why we shouldn’t put all our eggs in one basket when de-risking DMPK.
CYP2J2: An epoxygenase worth bothering about
Should a greater importance be placed on CYP2J2? In this blog post we explore the relevance of the mainly extrahepatic epoxygenase CYP2J2, given it's role at the crossroads of drug metabolism and endogenous bioactive oxy-lipid synthesis.
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.
