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

Details

Stereochemistry ACHIRAL
Molecular Formula C23H15F2NO2
Molecular Weight 375.3675
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BREQUINAR

SMILES

CC1=C(N=C2C=CC(F)=CC2=C1C(O)=O)C3=CC=C(C=C3)C4=C(F)C=CC=C4

InChI

InChIKey=PHEZJEYUWHETKO-UHFFFAOYSA-N
InChI=1S/C23H15F2NO2/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)

HIDE SMILES / InChI

Molecular Formula C23H15F2NO2
Molecular Weight 375.3675
Charge 0
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.

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
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:52:19 GMT 2023
Edited
by admin
on Sat Dec 16 16:52:19 GMT 2023
Record UNII
5XL19F49H6
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BREQUINAR
INN   MI   WHO-DD  
INN  
Official Name English
4-QUINOLINECARBOXYLIC ACID, 6-FLUORO-2-(2'-FLUORO(1,1'-BIPHENYL)-4-YL)-3-METHYL-
Common Name English
Brequinar [WHO-DD]
Common Name English
brequinar [INN]
Common Name English
6-FLUORO-2-(2'-FLUORO-4-BIPHENYLYL)-3-METHYL-4-QUINOLINECARBOXYLATE
Systematic Name English
BREQUINAR [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1557
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
NCI_THESAURUS C2169
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL38434
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
SMS_ID
100000088660
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
CHEBI
177387
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
NCI_THESAURUS
C1560
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
MERCK INDEX
m2646
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY Merck Index
EVMPD
SUB05885MIG
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
EPA CompTox
DTXSID00242165
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
DRUG BANK
DB03523
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
CAS
96187-53-0
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
WIKIPEDIA
Brequinar
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
PUBCHEM
57030
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
MESH
C046943
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
FDA UNII
5XL19F49H6
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
INN
6204
Created by admin on Sat Dec 16 16:52:20 GMT 2023 , Edited by admin on Sat Dec 16 16:52:20 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY