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=C(F)C=CC=C4
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
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
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: Page: p.1406, 1407 |
unhealthy, ADULT n = 1 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 1 Sources: Page: p.1406, 1407 |
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: Page: p.1406, 1407 |
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: Page: p.986 |
unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: Page: p.986 |
DLT: Thrombocytopenia, Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 20%) Sources: Page: p.986Thrombocytopenia (grade 3, 40%) |
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: Page: p.1406, 1407 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.1406, 1407 |
DLT: Maculopapular rash, Skin eruption... Other AEs: Thrombocytopenia... Dose limiting toxicities: Maculopapular rash (grade 3, 33.3%) Other AEs:Skin eruption (grade 3, 33.3%) Mucositis (grade 3, 33.3%) Thrombocytopenia (grade 3, 66.7%) Sources: Page: p.1406, 1407 |
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: Page: p.1407 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.1407 |
Other AEs: Anemia, Stomatitis... Other AEs: Anemia (grade 3, 25%) Sources: Page: p.1407Stomatitis (grade 3, 25%) Leucopenia (grade 2, 25%) Thrombocytopenia (grade 4, 50%) |
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: Page: p.1407 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.1407 |
Other AEs: Thrombocytopenia, Stomatitis... Other AEs: Thrombocytopenia (grade 3, 25%) Sources: Page: p.1407Stomatitis (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: Page: p.986 |
unhealthy, ADULT n = 1 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 1 Sources: Page: p.986 |
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: Page: p.1406, 1407 |
unhealthy, ADULT n = 1 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 1 Sources: Page: p.1406, 1407 |
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: Page: p.1406, 1407 |
unhealthy, ADULT n = 1 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 1 Sources: Page: p.1406, 1407 |
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: Page: p.1406, 1407 |
unhealthy, ADULT n = 1 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 1 Sources: Page: p.1406, 1407 |
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: Page: p.1406, 1407 |
unhealthy, ADULT n = 1 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 1 Sources: Page: p.1406, 1407 |
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: Page: p.986 |
unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: Page: p.986 |
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: Page: p.986 |
unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: Page: p.986 |
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: Page: p.1406, 1407 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.1406, 1407 |
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: Page: p.1406, 1407 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.1406, 1407 |
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: Page: p.1406, 1407 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.1406, 1407 |
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: Page: p.1406, 1407 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.1406, 1407 |
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: Page: p.1407 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.1407 |
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: Page: p.1407 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.1407 |
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: Page: p.1407 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.1407 |
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: Page: p.1407 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.1407 |
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: Page: p.1407 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.1407 |
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: Page: p.1407 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.1407 |
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.
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NCI_THESAURUS |
C2169
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C1557
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CHEMBL38434
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DTXSID30242173
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m2646
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C1078
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177871
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ACTIVE MOIETY
SUBSTANCE RECORD