Antitumor activity of brequinar sodium (Dup-785) against human head and neck squamous cell carcinoma xenografts.
The effect of Brequinar sodium on the growth of xenografts established from head and neck squamous cell carcinomas (HNSCC) was assessed. Brequinar sodium is a novel drug, known to inhibit dihydroorotic acid dehydrogenase (DHO-DH), resulting in a decrease of the pyrimidine de novo synthesis. The drug was administered i.p. to tumor-bearing nude mice, once a day, during 5 days at a maximum tolerated dose of 50 mg/kg/day. Statistically significant growth delaying effects were observed in 4 out of 5 lines tested. In 3 of these lines the effect was moderate and short lasting, whereas in one line (HNX-LP) tumor growth rate was totally inhibited for a 17-day period. In this line, Brequinar sodium was superior to 5 drugs known to be active in HNSCC patients. In two tumor lines DHO-DH activity could be measured and the results are in agreement with the concept that there is a relation between Brequinar sodium sensitivity and enzyme activity.
Braakhuis
B J
BJ
Department of Otolaryngology, Free University Hospital, Amsterdam, The Netherlands.
van Dongen
G A
GA
Peters
G J
GJ
van Walsum
M
M
Snow
G B
GB
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D000090722:Dihydroorotate Dehydrogenase; D004353:Drug Evaluation, Preclinical; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D044925:Oxidoreductases Acting on CH-CH Group Donors; D014183:Transplantation, Heterologous; D011798:Quinaldines
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D000090722:Dihydroorotate Dehydrogenase; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C046943:brequinar; D011798:Quinaldines