Late stage oxidation reactions using PolyCYPs®

Small changes to a structure through late stage functionalisation can have a large impact in achieving improved LLE and solubility of drugs. Hydroxyl groups are the most common functional group in drugs and can reduce clogP by >1 unit, as well as enhance metabolic stability. Other benefits such as increased potency and greater selectivity are also achievable through late stage hydroxylation.

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.

Lead diversification case study

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.

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.

For more information or to order a kit, email enquiries@hyphadiscovery.co.uk

Download a pdf of the PolyCYPs brochure here.