Activation of hypolipidaemic drugs to acyl-coenzyme A thioesters.
Compounds possessing the characteristics of CoA thioesters of the hypolipidaemic peroxisome proliferators clofibric acid, nafenopin and ciprofibrate were formed on incubation of the drugs with rat liver microsomal fractions, ATP and CoA. The reactivity of the drugs correlated with their pharmacological potency. It is proposed that the active species of these compounds are their acyl-CoA thioesters.
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002994:Clofibrate / Q000031:analogs & derivatives* / Q000378:metabolism*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D058607:Fibric Acids; D006868:Hydrolysis; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009255:Nafenopin / Q000031:analogs & derivatives / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013056:Spectrophotometry, Ultraviolet; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D000214:Acyl Coenzyme A; D058607:Fibric Acids; D011422:Propionates; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D009255:Nafenopin; C051513:clofibric acid-coenzyme A; C051514:ciprofibrate-coenzyme A; C051515:nafenopin-coenzyme A; D002995:Clofibric Acid; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; C019304:ciprofibrate; D002994:Clofibrate