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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.

 

Introducing oxygen into a drug candidate late in the optimisation process has several applications including exploration of SAR (structure-activity relationships) and the ability to access derivatives that may possess superior properties such as improved metabolic stability and LLE (ligand-lipophilicity efficiency). Biocatalysis can provide access to chemical space in a complementary manner to chemical synthesis and provide a “one-experiment” solution to accessing multiple derivatives in parallel. This poster illustrates the application of a new biocatalysis kit, PolyCYPs®, to enable parallel synthesis of hydroxylated derivatives of drugs.

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