The relation between inhibition of cell growth and of dihydroorotic acid dehydrogenase by brequinar sodium.

The growth inhibitory effects of Brequinar Sodium (DUP-785; NSC 368390) in 7 different cell lines were related to growth rates and to the inhibition of dihydroorotic acid dehydrogenase (DHO-DH) activity. IC50 values were between 0.2 and 5.8 microM; the fastest growing cell line was least sensitive. Despite a large variation in sensitivity, basal activity of DHO-DH showed little variation (only 2-fold) between the different cell lines. Residual activity of DHO-DH in the presence of Brequinar Sodium varied 30-fold. Drug sensitivity correlated with this residual DHO-DH activity; DHO-DH activity was only slightly inhibited by Brequinar Sodium in the most resistant lines, and almost completely in the most sensitive.