Expediting a Pre-Clinical
Component of Drug
Discovery, Production of
Key Metabolites via Ex vivo Syntheses
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 As an adjunct to standard organic synthetic approaches, Adesis scientists have developed expedient scale-up routes for metabolites by the use of porcine liver homogenates or perfused livers as an ex vivo reactor system. The rationale to use porcine hepatic components is based on i) high metabolic homology to human metabolism, ii) ready availability of fresh porcine hepatic components and iii) direct use of an experimental agent. This approach is not intended to substitute for total syntheses approaches, as much as it facilitates isolation of adequate quantities of key metabolites (milligrams to grams) for unambiguous structure determination and for initial in vitro and in vivo bioprofiling. Ex vivo synthesis is another research offering in the Adesis armamentarium of specialized chemistry tools. Metabolism of a drug is an obligatory process after it has reached the primary site of pharmacological action. Depending on the metabolic process(es) involved, the duration of a drug's primary action may be enhanced and/or untoward toxicities can occur. Thus, an orderly elimination process for foreign molecules is necessary. Mammalian drug and xenobiotic metabolism is primarily mediated by metabolic enzymes in the liver, and lesser degree in the kidneys, lungs and gastro-intestinal tract [1]. Such processes are defined as Phase I (functionalization processes involving cytochrome P450 oxidases[2,3]) and Phase II (conjugation reactions of aqueous solubilization moieties involving UDP-glucuronosyltransfer-ases[4] and glutathione S-transferases). The Phase II processes provide conjugates that facilitate elimination of the drugs. |
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Informex 2012
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Informex New Orleans - February 14-17, 2012
Come meet the Adesis team (Booth #946) or schedule a meeting prior to the show Schedule Meeting
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