PolyCYPs: Biocatalytic Tools for the Optimisation of Drug Leads
This poster illustrates the application of PolyCYPs biocatalysts to generate hydroxylated and other oxidised derivatives that complement conventional lead optimisation strategies.
PolyCYPs are recombinant cytochrome P450 enzymes cloned from talented bacteria in Hypha’s biotransformation panel. The production of multiple hydroxylated derivatives in parallel by PolyCYPs gives the opportunity to identify derivatives with improved properties.
The poster uses case studies to illustrate several potential benefits:
- Boost DMPK properties, particularly metabolic stability
- Empirically discover new polar interactions in binding sites, improving potency and selectivity
- Establish if metabolites are active before deprioritising a metabolically unstable scaffold
- Utilise hydroxylated derivatives/metabolites as handles for late stage functionalisation e.g. fluorination
- Rapidly expand polar SAR and broaden IP coverage, including the exemplification of active metabolites