Pentafluorobenzaldehyde: A new potent inhibitor of aldehyde dehydrogenase isoenzymes

D. W. Macomber, D. C. Mays, Susan Buckheister, J. J. Lipsky

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Pentafluorobenzaldehyde (1) has been found to be a potent inhibitor of both Class 1 and 2 aldehyde dehydrogenase isoenzymes, which are major enzymes involved in ethanol metabolism. Compound 1 inhibits human recombinant cytosolic ALDH1 activity towards acetaldehyde/NAD+ with an IC50 value of 1.6 μM, whereas human recombinant mitochondrial ALDH2 is inhibited similarly with an IC50 of 1 μM. By comparison, previous work from our laboratory (Biochemistry 36, 13748-13754, 1997) has shown, under similar conditions, the IC50 values for disulfiram were 0.15 and 1.45 μM, respectively. The inhibitory activity of 1 towards ALDH1 and ALDH2 using different aldehydes/NAD+ is proposed to occur by an alternative substrate process in which 1 forms a tight-binding complex with the ALDH isoenzymes with subsequent slow turnover (i.e. low Km and low Vmax). Therefore, compound 1 represents novel mechanism than that of disulfiram in inhibiting ALDH.

Original languageEnglish (US)
Pages (from-to)P40
JournalClinical pharmacology and therapeutics
Issue number2
StatePublished - Dec 1 2001


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