TY - JOUR
T1 - Pentafluorobenzaldehyde
T2 - A new potent inhibitor of aldehyde dehydrogenase isoenzymes
AU - Macomber, D. W.
AU - Mays, D. C.
AU - Buckheister, Susan
AU - Lipsky, J. J.
PY - 2001/12/1
Y1 - 2001/12/1
N2 - 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.
AB - 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.
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M3 - Article
AN - SCOPUS:33748964811
SN - 0009-9236
VL - 69
SP - P40
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 2
ER -