PolarExplorer – Late stage hydroxylation using PolyCYPs enzymes
Hypha’s PolyCYPs® enzymes provide a fast and easy way to hydroxylate aliphatic or aromatic moieties at multiple sites in parallel, including metabolically susceptible positions. Both CYP-derived human metabolites and other oxidised derivatives can then be accessed simultaneously for structure elucidation and biological testing.
PolyCYPs® enzymes in the kit have been cloned from some of the talented actinomycete bacteria in Hypha’s biotransformation panel, providing a wide diversity of CYPs that hydroxylate a variety of drug compounds.
In this case study, five active monohydroxylated derivatives of a client’s drug lead were produced using PolyCYPs, with a 56% conversion of the parent drug by the best PolyCYP enzyme, enabling access to polar chemical space in parallel as part of SAR studies. Access a pdf of the poster on “Late Stage Functionalization of Drug Candidates using PolyCYPS® Enzymes” here.
PolarExplorer process
Drug candidates are screened in client labs against PolyCYPs enzymes in the screening kit to identify isoforms undertaking the desired oxidation(s). For lipophilic compounds, a cyclodextrin-based formulation reagent is included to aid solubilisation. Scale-up vials of any specific isoform can then be ordered to generate more material for further testing.
This process can also be operated at Hypha as a service option if preferred, as undertaken for a European Pharma company who gave us the following feedback:
“We would like to mention that it has been a pleasure to work with Hypha in this project. We are really satisfied with how the collaboration has progressed, reaching the defined goals and timelines in a very efficient manner. Access of hydroxylated compounds through PolyCYPs has saved our company time and resources. We are sure that we will have more opportunities to work together in the future.”
Program Leader, European Pharma Company
For more information or to order a kit, email enquiries@hyphadiscovery.co.uk
