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Compound Detail

CHEMBL38434

BREQUINAR
🧪 Phase II
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🧪 Phase II
Cc1c(-c2ccc(-c3ccccc3F)cc2)nc2ccc(F)cc2c1C(=O)O
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL38434
Name BREQUINAR
Phase Phase II
Structure Type MOL
InChI Key PHEZJEYUWHETKO-UHFFFAOYSA-N

Known Names

Brequinar
87
Targets
141
Activities
3
Assay Types
18
PK Parameters
20
Publications
1
Known Names
2
Indications
1
Mechanisms

Molecular Properties

375.4
MW (Da)
5.85
ALogP
2
HBA
1
HBD
50.2
PSA (Ų)
0.49
QED
1
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral
USAN Year 1987

Extended Properties

Molecular Formula C23H15F2NO2
MW 375.37
Aromatic Rings 4
Heavy Atoms 28
NP-Likeness -0.90

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Dihydroorotate dehydrogenase inhibitor INHIBITOR Dihydroorotate dehydrogenase (quinone), mitochondrial ✓ ✓

Indications

Severe Acute Respiratory Syndrome Leukemia, Myeloid, Acute

Activity Summary

IC50 121 meas. best 9.32
EC50 19 meas. best 7.36
Ki 1 meas. best 7.92

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Dihydroorotate dehydrogenase (quinone), mitochondrial
CHEMBL1966
 IC50 9.32 8.14 0.5 25
Dihydrofolate reductase
CHEMBL202
 IC50 8.74 8.74 1.8 1
Dihydroorotate dehydrogenase (quinone), mitochondrial
CHEMBL1966
 Ki 7.92 7.92 12.0 1
ADMET
CHEMBL612558
 IC50 7.82 7.82 15.0 1
Dihydroorotate dehydrogenase (quinone), mitochondrial
CHEMBL2383
 IC50 7.48 6.9367 33.0 3
U-937
CHEMBL612794
 EC50 7.36 6.764 44.0 5
HCT-15
CHEMBL612263
 IC50 7.25 7.25 56.2 1
MOLM-13
CHEMBL3706572
 IC50 7.22 7.22 60.0 1
Western equine encephalitis virus
CHEMBL4513193
 EC50 7.11 7.11 78.0 1
Dengue virus
CHEMBL613757
 EC50 7.11 7.11 78.0 1
Vesicular stomatitis virus
CHEMBL613739
 EC50 7.11 6.815 78.0 2
Yellow fever virus
CHEMBL613731
 EC50 7.11 7.11 78.0 1
West Nile virus
CHEMBL613730
 EC50 7.11 7.11 78.0 1
MDA-MB-468
CHEMBL614335
 IC50 7.09 7.09 82.0 1
HCT-116
CHEMBL394
 IC50 7.06 6.2033 87.1 3
MOLT-4
CHEMBL614177
 IC50 7.05 7.05 89.1 1
THP-1
CHEMBL614245
 EC50 7.03 6.678 94.0 5
LOX IMVI
CHEMBL614096
 IC50 7.03 7.03 93.3 1
SARS-CoV-2
CHEMBL4303835
 EC50 6.91 6.91 123.0 1
NCI-H460
CHEMBL396
 IC50 6.89 6.89 128.8 1
K562
CHEMBL385
 IC50 6.84 6.555 144.5 2
ACHN
CHEMBL614519
 IC50 6.82 6.82 151.4 1
786-0
CHEMBL613102
 IC50 6.71 6.71 195.0 1
U-251
CHEMBL615022
 IC50 6.71 6.71 195.0 1
OCI-AML2
CHEMBL2366220
 IC50 6.7 6.7 200.0 1
Jurkat
CHEMBL397
 IC50 6.7 5.7 200.0 4
KM12
CHEMBL614709
 IC50 6.68 6.68 208.9 1
HT-1080
CHEMBL614580
 IC50 6.68 5.725 210.0 2
A549
CHEMBL392
 IC50 6.63 6.01 234.4 2
SF-295
CHEMBL614908
 IC50 6.62 6.62 239.9 1
DU-145
CHEMBL613508
 IC50 6.58 6.58 263.0 1
UACC-62
CHEMBL614610
 IC50 6.58 6.58 263.0 1
MCF7
CHEMBL387
 IC50 6.57 5.4867 269.1 3
CCRF-CEM
CHEMBL382
 IC50 6.55 6.55 281.8 1
IGROV-1
CHEMBL613984
 IC50 6.52 6.52 302.0 1
MDA-MB-231
CHEMBL400
 IC50 6.51 5.975 310.0 2
OVCAR-8
CHEMBL612555
 IC50 6.49 6.49 323.6 1
SF-539
CHEMBL614860
 IC50 6.46 6.46 346.7 1
SF-268
CHEMBL613977
 IC50 6.43 6.43 371.5 1
HT-29
CHEMBL384
 IC50 6.43 5.76 371.5 3
MDA-MB-435
CHEMBL614697
 IC50 6.43 6.43 371.5 1
RPMI-8226
CHEMBL614882
 IC50 6.43 6.43 371.5 1
SW-620
CHEMBL612262
 IC50 6.42 6.42 380.2 1
Unchecked
CHEMBL612545
 IC50 6.4 5.34 400.0 2
SR
CHEMBL614300
 IC50 6.37 6.37 426.6 1
Influenza A virus
CHEMBL613740
 EC50 6.34 6.34 460.0 1
Molecular identity unknown
CHEMBL612546
 EC50 6.29 6.29 510.0 1
COLO 205
CHEMBL614561
 IC50 6.29 6.29 512.9 1
HL-60
CHEMBL383
 IC50 6.26 6.26 544.0 1
M21
CHEMBL614117
 IC50 6.24 5.42 570.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 3200.0 ng.hr.mL-1 Homo sapiens
AUC 3800.0 ng.hr.mL-1 Homo sapiens
AUC 20700.0 ng.hr.mL-1 Homo sapiens
CL 3.2 L/hr/m2 Homo sapiens
CL 4.9 L/hr/m2 Homo sapiens
CL 0.2 mL.min-1.kg-1 Mus musculus
Cmax 4795.27 nM Homo sapiens
Cmax 7192.9 nM Homo sapiens
F 72.0 % Mus musculus
Fu 0.0039 - Homo sapiens
Fu 0.0073 - Mus musculus
T1/2 2.9 hr Homo sapiens
T1/2 3.1 hr Homo sapiens
T1/2 4.3 hr Homo sapiens
T1/2 1.0 hr Homo sapiens
T1/2 3.0 hr Homo sapiens
T1/2 3.0 hr Mus musculus
t1/2 - - Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 0.48 nM 9.32 Inhibition of human DHODH 33007394
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 1.8 nM 8.74 Inhibition of recombinant human N-terminal GST-fusion tagged DHODH expressed in ... 36162075
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 1.8 nM 8.74 Inhibition of human recombinant N-terminal GST-tagged DHODH expressed in Escheri... 33844533
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 1.8 nM 8.74 Inhibition of recombinant N-terminal GST-tagged human DHODH (31 to 395 residues)... 29939742
Dihydrofolate reductase IC50 = 1.8 nM 8.74 Inhibition of recombinant human N-terminal truncated GST-tagged DHFR (31 to 395 ... 28235702
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 3.0 nM 8.52 Inhibition of recombinant human DHODH by using blue indicator dye DCIP 20153645
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 4.0 nM 8.4 Inhibition of human recombinant DHODH 27994748
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 5.0 nM 8.3 Inhibition of recombinant N-terminal His-tagged human DHODH (31 to 395 residues)... 34516133
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 5.2 nM 8.28 Inhibition of human DHODH using dihydroorotate as substrate and CoQ10 as co-subs... 32496056
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 6.0 nM 8.22 Inhibition of human DHODH 23452331
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 7.3 nM 8.14 Inhibition of DHODH (unknown origin) expressed in Escherichia coli Rosetta2(DE3)... 29727569
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 7.4 nM 8.13 Inhibition of N-terminally truncated human DHODH (Met30 to Arg396 residues) expr... -
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 8.0 nM 8.1 Inhibitory activity against recombinant human DHODH 16246558
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 8.4 nM 8.08 Inhibition of human DHODH using dihydroorotate substrate by DCIP assay 30108840
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 8.45 nM 8.07 Method for Testing Activities of Compounds at Enzyme Level: Principles of activi... -
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 10.0 nM 8.0 Inhibition of human recombinant DHODH 26079043
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 10.0 nM 8.0 Inhibition of human purified recombinant DHODH 23452331
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 10.0 nM 8.0 Inhibition of human recombinant DHODH expressed in baculovirus infected insect c... 27994748
Dihydroorotate dehydrogenase (quinone), mitochondrial IC50 = 10.0 nM 8.0 Inhibition of human recombinant DHODH by Surface plasmon resonance based analysi... 38685143
Dihydroorotate dehydrogenase (quinone), mitochondrial Ki = 12.0 nM 7.92 Inhibition measurement of orotate formation from radiolabeled dihydroorotate, us... -

Literature References

PubMed DOI Target Context # Activities
32496056 10.1021/acs.jmedchem.0c00512 Raji 18
32212728 10.1021/acs.jmedchem.9b01658 Dihydroorotate dehydrogenase (quinone), mitochondrial 14
29727569 10.1021/acs.jmedchem.7b01862 Homo sapiens 13
33007394 10.1016/j.bmcl.2020.127589 ADMET 8
34516133 10.1021/acs.jmedchem.1c01402 Dihydroorotate dehydrogenase (quinone), mitochondrial 8
29939742 10.1021/acs.jmedchem.8b00373 THP-1 7
29727569 10.1021/acs.jmedchem.7b01862 HCT-116 5
29939742 10.1021/acs.jmedchem.8b00373 U-937 5
- 10.6019/CHEMBL4651402 SARS-CoV-2 4
23452331 10.1021/jm301848w Dihydroorotate dehydrogenase (quinone), mitochondrial 4
33007554 10.1016/j.bmc.2020.115739 HT-29 3
28235702 10.1016/j.ejmech.2017.02.017 Jurkat 3
29727569 10.1021/acs.jmedchem.7b01862 No relevant target 3
29939742 10.1021/acs.jmedchem.8b00373 Jurkat 3
33007554 10.1016/j.bmc.2020.115739 MCF7 3
32496056 10.1021/acs.jmedchem.0c00512 No relevant target 3
29939742 10.1021/acs.jmedchem.8b00373 PBMC 3
30776695 10.1016/j.ejmech.2019.02.018 Dihydroorotate dehydrogenase (quinone), mitochondrial 3
29939742 10.1021/acs.jmedchem.8b00373 No relevant target 3
32212728 10.1021/acs.jmedchem.9b01658 ADMET 2

Data from ChEMBL 36 via Core Engine