An in situ pig liver esterase assay as a useful predictive tool for the likely in vitro anti viral activity of phosphoramidate pro-drugs.
The pig liver esterase (PLE) assay has been designed to "reproduce" in vitro the first step of the metabolism of phosphoramidate pro-drugs that generates the free amino acyl phosphoramidate intermediate which has been described as a key metabolite necessary but not sufficient for the biological activity. The method could be used as a predictive tool for the likely in vitro biological activity as well as for Structure-Activity Relationship establishment (SAR).
Ballatore
C
C
Welsh School of Pharmacy, Cardiff University, UK.
McGuigan
C
C
De Clercq
E
E
Balzarini
J
J
D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004950:Esterases / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine
D019380:Anti-HIV Agents; D009943:Organophosphorus Compounds; D011355:Prodrugs; D004950:Esterases