BREQUINAR

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 Search

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

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=40886 | http://en.pharmacodia.com/yaodu/html/v1/chemicals/27908be590d3ec381df976ecbf65df81.html | https://www.ncbi.nlm.nih.gov/pubmed/8623481

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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dihydroorotate dehydrogenase 9 Target ID: CHEMBL1966 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9802339 \| https://www.ncbi.nlm.nih.gov/pubmed/26079043 \| https://www.ncbi.nlm.nih.gov/pubmed/8687451	Inhibitor 8297		10.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Advanced melanoma 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1450049	Primary	Phase II 1132	Unknown Approved Use Unknown
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2306795 https://www.ncbi.nlm.nih.gov/pubmed/9740540	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8256771	Primary	Phase II 1132	Unknown Approved Use 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: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/8499153 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: https://pubmed.ncbi.nlm.nih.gov/8499153 Page: p.986	DLT: Thrombocytopenia, Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 20%) Thrombocytopenia (grade 3, 40%) Sources: https://pubmed.ncbi.nlm.nih.gov/8499153 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: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/2591433 Page: p.1407	Other AEs: Thrombocytopenia, Stomatitis... Other AEs: Thrombocytopenia (grade 3, 25%) Stomatitis (grade 3, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/2591433 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: https://pubmed.ncbi.nlm.nih.gov/8499153 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: https://pubmed.ncbi.nlm.nih.gov/8499153 Page: p.986	Sources: https://pubmed.ncbi.nlm.nih.gov/8499153 Page: p.986

AEs

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY113766	https://www.001chemical.com/chem/search?q=DY113766
1PlusChem LLC	1P006SVQ	https://www.1pchem.com/search?query=1P006SVQ
A2B Chem	AD16566	http://a2bchem.com/prod/AD16566
A2B Chem	AI68899	http://a2bchem.com/prod/AI68899
AA Blocks	AA006SCA	http://aablocks.com/goods/Goods/detail?id=AA006SCA
AK Scientific	X5917	https://aksci.com/item_detail.php?cat=X5917
Achemo Scientific Limited	AC-89615	http://www.achemo.com/search/?Keyword=AC-89615
Alfa Chemistry	278939	http://www.alfa-chemistry.com/search.aspx?q=278939
Alfa Chemistry	ACM96201886	http://www.alfa-chemistry.com/search.aspx?q=ACM96201886
Ambeed	A155500	http://www.ambeed.com/search/Search.html?keyword=A155500
Ambeed	A207630	http://www.ambeed.com/search/Search.html?keyword=A207630
AstaTech	F52273	http://astatechinc.com/CPSResult.php?CRNO=F52273
BLD Pharm	BD116738	http://www.bldpharm.com/search/Search.html?keyword=BD116738
BLD Pharm	BD118679	http://www.bldpharm.com/search/Search.html?keyword=BD118679
BOC Sciences	96187-53-0	http://www.bocsci.com/description.asp?cas=96187-53-0
BOC Sciences	96201-88-6	http://www.bocsci.com/description.asp?cas=96201-88-6
Chem Scene	CS-7842	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-7842
ChemShuttle	101293	https://www.chemshuttle.com/catalogsearch/result/?q=101293
Combi-Blocks	QN-0134	http://www.combi-blocks.com/cgi-bin/find.cgi?QN-0134
Debye Scientific	DB-080409	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-080409
Enamine	EN300-263943	https://www.enaminestore.com/catalog/EN300-263943
Excenen	EX-A1515	http://www.excenen.com/searchresultlist.php?id=EX-A1515
Fluorochem	80292	http://www.fluorochem.co.uk/Products/Product?code=080292
Fluoropharm	YF10042	http://www.fluoropharm.com/product/YF10042.html
KeyOrganics	AS-74463	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74463
KeyOrganics	DS-15411	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=DS-15411
Lab Network	LN00191481	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00191481
Lab Network	LN03271013	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN03271013
Lab Seeker	SC-55381	http://www.labseeker.com/search.php?keywords=SC-55381&category=0
Matrix Scientific	93124	http://www.matrixscientific.com/093124.html
MedChem Express	HY-108325	https://www.medchemexpress.com/search.html?q=HY-108325&ft=&fa=&fp=
MolPort	MolPort-006-169-119	https://www.molport.com/shop/molecule-link/MolPort-006-169-119
MolPort	MolPort-028-720-353	https://www.molport.com/shop/molecule-link/MolPort-028-720-353
Molcore	MC113766	http://www.molcore.com/CatMC113766.html
MuseChem	M008880	https://www.musechem.com/product/M008880.html
ShangHai Biochempartner	BCP06006	http://www.biochempartner.com/search_BCP06006
TargetMol	T5013	https://www.targetmol.com/search?keyword=T5013
eMolecules	300620155	https://orderbb.emolecules.com/search/#?query=300620155
eMolecules	43451776	https://orderbb.emolecules.com/search/#?query=43451776
eMolecules	44786255	https://orderbb.emolecules.com/search/#?query=44786255
eNovation Chemicals	D621765	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D621765&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D759561	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D759561&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-7590091357	https://mcule.com/MCULE-7590091357/
mcule	MCULE-7868113779	https://mcule.com/MCULE-7868113779/

PubMed

Title	Date	PubMed
Phase I clinical and pharmacokinetic trial of Brequinar sodium (DuP 785; NSC 368390).	1989 Aug 15	2743343
Structural and functional comparison of agents interfering with dihydroorotate, succinate and NADH oxidation of rat liver mitochondria.	1998 Oct 15	9776318
Immunosuppressive drugs: the first 50 years and a glance forward.	2000 May	10878284

Patents

Sample Use Guides

In Vivo Use Guide

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

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