Pharmacokinetics of Brequinar sodium (NSC 368390) in patients with solid tumors during a phase I study.

  title={Pharmacokinetics of Brequinar sodium (NSC 368390) in patients with solid tumors during a phase I study.},
  author={Gilberto Schwartsmann and Wim J.F. van der Vijgh and M B van Hennik and Ina Klein and Jan Baptist Vermorken and Pierre F. Dodion and Wim W. ten Bokkel Huinink and G Joggi and Helen E. Gall and Nadine Crespeigne},
  journal={European journal of cancer \& clinical oncology},
  volume={25 12},
Re-evaluation of Brequinar sodium, a dihydroorotate dehydrogenase inhibitor
  • G. Peters
  • Medicine, Chemistry
    Nucleosides, nucleotides & nucleic acids
  • 2018
DUP-785 was inactive against solid tumors, but DHO-DH inhibition was associated with myeloid toxicity, which may explain its potential for treatment of leukemia or inflammatory diseases.
Phase I Safety and Pharmacokinetic Studies of Brequinar Sodium after Single Ascending Oral Doses in Stable Renal, Hepatic, and Cardiac Allograft Recipients
Safety results indicate that BQR was well tolerated by this patient population, and the pharmacokinetics of single oral 0.5‐ to 4‐mg/kg doses of B QR were characterized by a lower oral clearance than that seen in previous studies in patients with cancer.
Clinical Phase I and Pharmacology Study of Gemcitabine (2', 2'-Difluorodeoxycytidine) Administered in a Two-Weekly Schedule
dC was rapidly eliminated in contrast to dFdU, which was present for at least 18 h, as well as dFDCTP in lymphocytes, in a Phase I trial of gemcitabine in refractory solid cancer.
In vivo inhibition of the pyrimidine de novo enzyme dihydroorotic acid dehydrogenase by brequinar sodium (DUP-785; NSC 368390) in mice and patients.
The extent of the depletion and of the accompanying rebound of uridine levels and the extent and duration of DHO-DH inhibition in the individual patients could be partially associated with drug toxicity in these patients.
Protein binding of brequinar in the plasma of healthy donors and cancer patients and analysis of the relationship between protein binding and pharmacokinetics in cancer patients
Examination of relationships between the unbound brequinar fraction and pharmacokinetics suggested that plasma protein binding was not a major determinant of brequinars disposition in cancer patients.
Synthesis and immunosuppressant activity of pyrazole carboxamides.
A Carboxylic Acid Isostere Screen of the DHODH Inhibitor Brequinar.


Comparative pharmacokinetics of cisplatin and three analogues in mice and humans.
The results suggest that the AUCp/AUCm ratio of free platinum over the first part of the concentration versus time curve can possibly be used to predict the maximal tolerated dose of platinum analogues in humans, during the early stage of phase I studies.
Activity of a novel 4-quinolinecarboxylic acid, NSC 368390 [6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarb oxylic acid sodium salt], against experimental tumors.
A novel, substituted 4-quinolinecarboxylic acid (NSC 368390) demonstrated antitumor activity against L1210 leukemia and B16 melanoma in the National Cancer Institute's Developmental Therapeutics Program and is being developed as a Phase 1 anticancer agent.
Biochemical strategy of cancer cells and the design of chemotherapy: G. H. A. Clowes Memorial Lecture.
  • G. Weber
  • Philosophy, Medicine
    Cancer research
  • 1983
L'essence et the substance des progres theoriques and experimentaux vers une connaissance de la strategie biochimique et de the logique de l'expression des genes dans les cellules cancereuses et on identifie un programme enzymatique et metabolique commun dansles diverses tumeurs animales and humaines.
Purine and pyrimidine metabolism in peripheral blood lymphocytes.
Mechanism of action of the novel anticancer agent 6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarbo xylic acid sodium salt (NSC 368390): inhibition of de novo pyrimidine nucleotide biosynthesis.
This study demonstrates that NSC 368390 exerts its tumoricidal effect by inhibiting a step in de novo pyrimidine biosynthesis resulting in the depletion of critical precursors for RNA and DNA synthesis.