Often several strategies are needed to access all key metabolites observed during drug development programs. Hypha has developed a “one-stop metabolite shop” scheme, which utilizes a combination of biological and chemical techniques in order to fulfil requirements to access any type of metabolites.
The one-stop metabolite concept offers a parallel or sequential screening step to identify the most productive and cost-effective method to produce target metabolites. Depending on the type and quantity of metabolite required, a combination of chemical synthesis, mammalian S9, microbial biotransformation and recombinant phase I enzymes can be employed. Once the optimal production system is identified, the method can be scaled up to provide up to tens of grams of purified metabolites.
The synergy of using the one-stop shop concept to access metabolites will be exemplified using recent client case studies.
Case studies include:
- S9 fraction biotransformation to a scalable late-stage chemical synthesis of a major human N-glucuronide metabolite of LEO Compound 1
Scale-up of gram amounts of a hydroxylated metabolite produced by PolyCYPs 152