U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of BREQUINAR SODIUM

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

HIDE SMILES / InChI
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse 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%)
Leucopenia (grade 2, 100%)
AEs leading to
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%)
Thrombocytopenia (grade 3, 40%)
Sources: Page: p.986
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%)
Skin eruption (grade 3, 33.3%)
Mucositis (grade 3, 33.3%)
Other AEs:
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%)
Stomatitis (grade 3, 25%)
Leucopenia (grade 2, 25%)
Thrombocytopenia (grade 4, 50%)
Sources: Page: p.1407
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%)
Stomatitis (grade 3, 25%)
Sources: Page: p.1407
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

AEs

AESignificanceDosePopulation
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
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Structural and functional comparison of agents interfering with dihydroorotate, succinate and NADH oxidation of rat liver mitochondria.
1998 Oct 15
Patents

Patents

Sample Use Guides

Advanced melanoma: Brequinar was given at a median weekly dose of 1200 mg/m2 intravenously.
Route of Administration: Intravenous
In Vitro Use Guide
10 uM of brequinar sodium completely inhibited the dihydroorotate-induced oxygen consumption of rat liver mitochondria.
Name Type Language
BREQUINAR SODIUM
MART.   USAN   WHO-DD  
USAN  
Official Name English
BREQUINAR SODIUM [USAN]
Common Name English
4-QUINOLINECARBOXYLIC ACID, 6-FLUORO-2-(2'-FLUORO(1,1'-BIPHENYL)-4-YL)-3-METHYL-, SODIUM SALT
Common Name English
NSC-368390
Code English
Brequinar sodium [WHO-DD]
Common Name English
BREQUINAR SODIUM [MART.]
Common Name English
BREQUINAR SODIUM SALT [MI]
Common Name English
BREQUINAR SODIUM SALT
MI  
Common Name English
DUP 785
Code English
6-FLUORO-2-(2'-FLUORO-1,1'-BIPHENYL-4-YL)-3-METHYL-4-QUINOLINECARBOXYLIC ACID SODIUM
Systematic Name English
DUP-785
Code English
Classification Tree Code System Code
NCI_THESAURUS C2169
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
NCI_THESAURUS C1557
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL38434
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY
EPA CompTox
DTXSID30242173
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY
MERCK INDEX
m2646
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY Merck Index
PUBCHEM
23663964
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY
DRUG BANK
DBSALT002498
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY
FDA UNII
49EEF6HRUS
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY
USAN
Z-2
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY
NCI_THESAURUS
C1078
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY
CHEBI
177871
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY
CAS
96201-88-6
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY
NSC
368390
Created by admin on Fri Dec 15 15:33:19 GMT 2023 , Edited by admin on Fri Dec 15 15:33:19 GMT 2023
PRIMARY