title: Antitumor activity of brequinar sodium (Dup-785) against human head and neck squamous cell carcinoma xenografts.
abstract: 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.
authors.affiliation: Department of Otolaryngology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: B J
authors.initials: BJ
authors.lastname: Braakhuis
authors.forename: G A
authors.initials: GA
authors.lastname: van Dongen
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
authors.forename: M
authors.initials: M
authors.lastname: van Walsum
authors.forename: G B
authors.initials: GB
authors.lastname: Snow
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D000090722:Dihydroorotate Dehydrogenase; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C046943:brequinar; D011798:Quinaldines