Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C23H14F2NO2.Na |
| Molecular Weight | 397.3493 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].CC1=C(N=C2C=CC(F)=CC2=C1C([O-])=O)C3=CC=C(C=C3)C4=CC=CC=C4F
InChI
InChIKey=PZOHOALJQOFNTB-UHFFFAOYSA-M
InChI=1S/C23H15F2NO2.Na/c1-13-21(23(27)28)18-12-16(24)10-11-20(18)26-22(13)15-8-6-14(7-9-15)17-4-2-3-5-19(17)25;/h2-12H,1H3,(H,27,28);/q;+1/p-1
| Molecular Formula | Na |
| Molecular Weight | 22.98976928 |
| Charge | 1 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C23H14F2NO2 |
| Molecular Weight | 374.3596 |
| Charge | -1 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Brequinar is a synthetic quinolinecarboxylic acid analogue with antineoplastic properties. Brequinar inhibits the enzyme dihydroorotate dehydrogenase, thereby blocking de novo pyrimidine biosynthesis. This agent may also enhance the in vivo antitumor effect of antineoplastic agents such as 5-FU. Brequinar had been in phase II clinical trials by Bristol-Myers Squibb for the treatment of cancer and transplant rejection. However, this research has been discontinued.
Brequinar had been also in preclinical studys for the treatment of cytomegalovirus infections. However, this research has been discontinued.
Originator
Sources: http://en.pharmacodia.com/yaodu/html/v1/chemicals/27908be590d3ec381df976ecbf65df81.html
Curator's Comment: # Bristol-Myers Squibb
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
30.6 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8499153 |
170 mg/m² single, intravenous dose: 170 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
BREQUINAR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
54 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8499153 |
170 mg/m² single, intravenous dose: 170 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
BREQUINAR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2.1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8499153 |
170 mg/m² single, intravenous dose: 170 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
BREQUINAR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7987984 |
BREQUINAR plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
2600 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 2600 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 2600 mg/m2, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Thrombocytopenia, Leucopenia... Disc. AE: Anemia... Other AEs: Stomatitis... Dose limiting toxicities: Thrombocytopenia (grade 4, 100%) AEs leading toLeucopenia (grade 2, 100%) discontinuation/dose reduction: Anemia (grade 1, 100%) Other AEs:Stomatitis (grade 3, 100%) Sources: |
210 mg/m2 1 times / day multiple, intravenous MTD Dose: 210 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 210 mg/m2, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Thrombocytopenia, Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 3, 40%) Sources: Thrombocytopenia (grade 4, 20%) |
2300 mg/m2 1 times / week multiple, intravenous MTD Dose: 2300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 2300 mg/m2, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
DLT: Skin eruption, Maculopapular rash... Other AEs: Thrombocytopenia... Dose limiting toxicities: Skin eruption (grade 3, 33.3%) Other AEs:Maculopapular rash (grade 3, 33.3%) Mucositis (grade 3, 33.3%) Thrombocytopenia (grade 3, 66.7%) Sources: |
600 mg/m2 2 times / week multiple, intravenous MTD Dose: 600 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 600 mg/m2, 2 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Other AEs: Thrombocytopenia, Leucopenia... Other AEs: Thrombocytopenia (grade 4, 50%) Sources: Leucopenia (grade 2, 25%) Anemia (grade 3, 25%) Stomatitis (grade 3, 25%) |
850 mg/m2 2 times / week multiple, intravenous MTD Dose: 850 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 850 mg/m2, 2 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Other AEs: Thrombocytopenia, Stomatitis... Other AEs: Thrombocytopenia (grade 3, 25%) Sources: Stomatitis (grade 3, 25%) |
350 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 350 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 350 mg/m2, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Anemia | grade 1, 100% Disc. AE |
2600 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 2600 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 2600 mg/m2, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Leucopenia | grade 2, 100% DLT, Disc. AE |
2600 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 2600 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 2600 mg/m2, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Stomatitis | grade 3, 100% | 2600 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 2600 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 2600 mg/m2, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Thrombocytopenia | grade 4, 100% DLT, Disc. AE |
2600 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 2600 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 2600 mg/m2, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Thrombocytopenia | grade 3, 40% DLT |
210 mg/m2 1 times / day multiple, intravenous MTD Dose: 210 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 210 mg/m2, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Thrombocytopenia | grade 4, 20% DLT |
210 mg/m2 1 times / day multiple, intravenous MTD Dose: 210 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 210 mg/m2, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Maculopapular rash | grade 3, 33.3% DLT, Disc. AE |
2300 mg/m2 1 times / week multiple, intravenous MTD Dose: 2300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 2300 mg/m2, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Mucositis | grade 3, 33.3% DLT, Disc. AE |
2300 mg/m2 1 times / week multiple, intravenous MTD Dose: 2300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 2300 mg/m2, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Skin eruption | grade 3, 33.3% DLT, Disc. AE |
2300 mg/m2 1 times / week multiple, intravenous MTD Dose: 2300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 2300 mg/m2, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Thrombocytopenia | grade 3, 66.7% | 2300 mg/m2 1 times / week multiple, intravenous MTD Dose: 2300 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 2300 mg/m2, 1 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Leucopenia | grade 2, 25% | 600 mg/m2 2 times / week multiple, intravenous MTD Dose: 600 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 600 mg/m2, 2 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Anemia | grade 3, 25% | 600 mg/m2 2 times / week multiple, intravenous MTD Dose: 600 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 600 mg/m2, 2 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Stomatitis | grade 3, 25% | 600 mg/m2 2 times / week multiple, intravenous MTD Dose: 600 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 600 mg/m2, 2 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Thrombocytopenia | grade 4, 50% | 600 mg/m2 2 times / week multiple, intravenous MTD Dose: 600 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 600 mg/m2, 2 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Stomatitis | grade 3, 25% | 850 mg/m2 2 times / week multiple, intravenous MTD Dose: 850 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 850 mg/m2, 2 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Thrombocytopenia | grade 3, 25% | 850 mg/m2 2 times / week multiple, intravenous MTD Dose: 850 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 850 mg/m2, 2 times / week Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Immunosuppressive drugs: the first 50 years and a glance forward. | 2000-05 |
|
| Structural and functional comparison of agents interfering with dihydroorotate, succinate and NADH oxidation of rat liver mitochondria. | 1998-10-15 |
|
| Phase I clinical and pharmacokinetic trial of Brequinar sodium (DuP 785; NSC 368390). | 1989-08-15 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1450049
Advanced melanoma: Brequinar was given at a median weekly dose of 1200 mg/m2 intravenously.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9776318
10 uM of brequinar sodium completely inhibited the dihydroorotate-induced oxygen consumption of rat liver mitochondria.
| Substance Class |
Chemical
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Mon Mar 31 18:01:01 GMT 2025
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| Record UNII |
49EEF6HRUS
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Validated (UNII)
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C2169
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NCI_THESAURUS |
C1557
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CHEMBL38434
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DTXSID30242173
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m2646
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300000055287
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23663964
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DBSALT002498
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49EEF6HRUS
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Z-2
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177871
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96201-88-6
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368390
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