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.
de Kant
E
E
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
Pinedo
H M
HM
Laurensse
E
E
Peters
G J
GJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D004081:Dihydroorotate Oxidase / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D051381:Rats; D014407:Tumor Cells, Cultured; D011798:Quinaldines
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D004081:Dihydroorotate Oxidase; D010088:Oxidoreductases; C046943:brequinar; D011798:Quinaldines