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

Details

Stereochemistry ABSOLUTE
Molecular Formula C19H19FN4O3
Molecular Weight 370.3776
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BRIVANIB

SMILES

C[C@@H](O)COC1=CN2N=CN=C(OC3=C(F)C4=C(NC(C)=C4)C=C3)C2=C1C

InChI

InChIKey=WCWUXEGQKLTGDX-LLVKDONJSA-N
InChI=1S/C19H19FN4O3/c1-10-6-13-14(23-10)4-5-15(17(13)20)27-19-18-12(3)16(26-8-11(2)25)7-24(18)22-9-21-19/h4-7,9,11,23,25H,8H2,1-3H3/t11-/m1/s1

HIDE SMILES / InChI
Molecular Formula C19H19FN4O3
Molecular Weight 370.3776
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created using several sources including: https://www.ncbi.nlm.nih.gov/pubmed/16570908 | https://www.ncbi.nlm.nih.gov/pubmed/18829493 | https://www.ncbi.nlm.nih.gov/pubmed/21349999 | https://www.ncbi.nlm.nih.gov/pubmed/22238246 | http://www.hrsa.gov/opa/programrequirements/orphandrugexclusion/orphandruglistarchived.pdf

Brivanib is a pyrrolotriazine-based compound and an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) with potential antineoplastic activity. It specifically targets and strongly binds to human VEGFR-2, a tyrosine kinase receptor and pro-angiogenic growth factor expressed almost exclusively on vascular endothelial cells. Blockade of VEGFR-2 by this agent may lead to an inhibition of VEGF-stimulated endothelial cell migration and proliferation, thereby inhibiting tumor angiogenesis. Brivanib has a moderate potency compared to VEGFR-2 against VEGFR-1 and FGFR-1 as well. Brivanib is suggested to be efficient in treatment of hepatocellular carcinoma (HCC). As first-line and as second-line therapy brivanib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, unresectable HCC in phase II clinical trials. On 3 march 2011, orphan designation was granted by the European Commission to Bristol-Myers Squibb for brivanib alaninate for the treatment of hepatocellular carcinoma.[

Originator

Bristol-Myers Squibb
145
Curator's Comment: # Bristol-Myers Squibb

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 3.0 nM [Kd]
Inhibitor
8297
 1039.0 nM [Kd]
Inhibitor
8297
 1892.0 nM [Kd]
Vascular endothelial growth factor receptor 2
104
Target ID: P35968
Gene ID: 3791.0
Gene Symbol: KDR
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 25.0 nM [IC50]
Vascular endothelial growth factor receptor 1
41
Target ID: P17948|||B3FR89
Gene ID: 2321.0
Gene Symbol: FLT1
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 0.38 µM [IC50]
Fibroblast growth factor receptor 1
45
Target ID: P11362|||Q14307|||Q9UDF2
Gene ID: 2260.0
Gene Symbol: FGFR1
Target Organism: Homo sapiens (Human)
Inhibitor
8297
 0.148 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
656
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
6610 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21131369
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BRIVANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2847 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21461891
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BRIVANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
62813 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21131369
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BRIVANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
53685 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21461891
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BRIVANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.3 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21131369
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BRIVANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
18.3 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21461891
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
BRIVANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1000 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
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/21131369
Page: p.1415
DLT: Mental status changes, Fatigue...
Other AEs: Arterial hypertension...
Dose limiting toxicities:
Mental status changes (grade 3, 25%)
Fatigue (grade 3, 25%)
Other AEs:
Arterial hypertension (grade 3-4, 25%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
unhealthy, ADULT
n = 20
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 20
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
Other AEs: Dizziness, ALT increased...
Other AEs:
Dizziness (grade 3-4, 5%)
ALT increased (grade 3-4, 15%)
AST increased (grade 3-4, 5%)
Fatigue (grade 3-4, 15%)
Arterial hypertension (grade 3-4, 15%)
Diarrhea (grade 3-4, 10%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Disc. AE: Cardio-respiratory arrest, Cerebral infarction...
AEs leading to
discontinuation/dose reduction:
Cardio-respiratory arrest (grade 5, 0.17%)
Cerebral infarction (grade 5, 0.17%)
Hepatic failure (grade 5, 0.17%)
Diarrhea (grade 5, 0.17%)
Upper gastrointestinal hemorrhage (grade 5, 0.17%)
Asthenia (grade 5, 0.17%)
Cerebrovascular accident (grade 5, 0.17%)
Hematemesis (grade 5, 0.17%)
Gastrointestinal hemorrhage (grade 5, 0.17%)
Skin disorder (2%)
Fatigue (5%)
Hyponatremia (2%)
Decreased appetite (2%)
Hyperbilirubinemia (2%)
Skin disorder (3%)
AST increased (2%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
unhealthy, ADULT
n = 595
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 595
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
Disc. AE: Dyspnoea, Cerebral haemorrhage...
AEs leading to
discontinuation/dose reduction:
Dyspnoea (1.8%)
Cerebral haemorrhage (grade 5, 0.17%)
Intracranial haemorrhage (grade 5, 0.17%)
Hypovolemic shock (grade 5, 0.17%)
Multi-organ failure (grade 5, 0.17%)
Bowel perforation (grade 5, 0.17%)
Pulmonary haemorrhage (grade 5, 0.17%)
Vomiting (1.8%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
AEs

AEs

AESignificanceDosePopulation
Fatigue grade 3, 25%
DLT
1000 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
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/21131369
Page: p.1415
Mental status changes grade 3, 25%
DLT
1000 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
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/21131369
Page: p.1415
Arterial hypertension grade 3-4, 25%
1000 mg 1 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
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/21131369
Page: p.1415
Diarrhea grade 3-4, 10%
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
unhealthy, ADULT
n = 20
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 20
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
ALT increased grade 3-4, 15%
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
unhealthy, ADULT
n = 20
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 20
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
Arterial hypertension grade 3-4, 15%
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
unhealthy, ADULT
n = 20
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 20
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
Fatigue grade 3-4, 15%
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
unhealthy, ADULT
n = 20
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 20
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
AST increased grade 3-4, 5%
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
unhealthy, ADULT
n = 20
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 20
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
Dizziness grade 3-4, 5%
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
unhealthy, ADULT
n = 20
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 20
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Page: p.1415
AST increased 2%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Decreased appetite 2%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Hyperbilirubinemia 2%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Hyponatremia 2%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Skin disorder 2%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Skin disorder 3%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Fatigue 5%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Asthenia grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Cardio-respiratory arrest grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Cerebral infarction grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Cerebrovascular accident grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Diarrhea grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Gastrointestinal hemorrhage grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Hematemesis grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Hepatic failure grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Upper gastrointestinal hemorrhage grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
unhealthy, ADULT
n = 575
Health Status: unhealthy
Condition: hepatocellular carcinoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 575
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Page: p.3520-3522
Dyspnoea 1.8%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
unhealthy, ADULT
n = 595
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 595
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
Vomiting 1.8%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
unhealthy, ADULT
n = 595
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 595
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
Bowel perforation grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
unhealthy, ADULT
n = 595
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 595
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
Cerebral haemorrhage grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
unhealthy, ADULT
n = 595
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 595
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
Hypovolemic shock grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
unhealthy, ADULT
n = 595
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 595
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
Intracranial haemorrhage grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
unhealthy, ADULT
n = 595
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 595
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
Multi-organ failure grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
unhealthy, ADULT
n = 595
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 595
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
Pulmonary haemorrhage grade 5, 0.17%
Disc. AE
800 mg 1 times / day multiple, oral
MTD
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
unhealthy, ADULT
n = 595
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 595
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Page: p.137
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inducer
781

substrate
1737

inhibitor
1587
substrate
1037

inhibitor
1767
inhibitor
1852

substrate
1217
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
MRP1
106

CYP2C8
911

CYP3A5
73

CYP1A2
1524

CYP2B6
810

P-gp
1461

CYP2C19
1478

BCRP
699
CYP1A2
1054

SULTs
3

CYP1A1
349

CYP2C19
991

P-gp
1537

SULT1A3
27

CYP1B1
92

BCRP
561

SULT2A1
24

CYP2C8
693

MRP1
107

SULT1A1
29

CYP2A6
543

SULT1E1
17

SULT1B1
5

CYP3A5
395

CYP2B6
664
CYP1A2
701

CYP2B6
547

P-gp
257

BCRP
75

MRP1
48
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2B6
1001
 likely
CYP3A4
1925
 likely
CYP1A2
1692
 minor [IC50 44.5 uM]
P-gp
1650
 moderate [IC50 18.4 uM]
CYP3A4
1925
 moderate [IC50 26.2 uM]
CYP2D6
1891
 moderate [IC50 34.7 uM]
CYP3A5
130
 no
BCRP
773
 weak
MRP1
172
 weak
P-gp
1650
 weak
CYP2C9
1819
 yes [IC50 1.39 uM]
MRP1
172
 yes [IC50 25.3 uM]
CYP2C8
965
 yes [IC50 3.08 uM]
CYP2C19
1553
 yes [IC50 3.64 uM]
CYP2B6
1001
 yes [IC50 5.95 uM]
BCRP
773
 yes [IC50 6.98 uM]
CYP1A2
1692
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1737
 major [Km 32.7 uM]
CYP1A2
1054
 major [Km 45 uM]
CYP2A6
543
 minor
CYP2B6
664
 minor
CYP2C19
991
 minor
CYP2C8
693
 minor
CYP2C9
1037
 minor
CYP2D6
1217
 minor
CYP3A5
395
 minor
SULT1A3
27
 minor
SULT2A1
24
 minor
BCRP
561
 no
MRP1
107
 no
P-gp
1537
 no
CYP1A1
349
 yes
CYP1B1
92
 yes
SULT1A1
29
 yes
SULT1B1
5
 yes
SULT1E1
17
 yes
SULTs
3
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
PubMed

PubMed

TitleDatePubMed
Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor.
2006 Apr 6
Discovery and validation of biomarkers that respond to treatment with brivanib alaninate, a small-molecule VEGFR-2/FGFR-1 antagonist.
2007 Jul 15
By looking back we can see the way forward: enhancing the gains achieved with antihormone therapy.
2008
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma.
2011 Apr 1
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
Patents

Patents

US20150297603
2
US6869952
2
US7932383
2

Sample Use Guides

In Vivo Use Guide
800 mg brivanib once daily until disease progression or toxicity treatment for liver cancer in Asian patients who have failed or could not tolerate sorafenib therapy
Route of Administration: Oral
In Vitro Use Guide
The SK-HEP1 and HepG2 cells were used to investigate the effects of brivanib on the VEGFR-2 and FGFR-1 signaling pathways in vitro.To study the effects of brivanib treatment on VEGF- and bFGF-stimulated activation of Akt and ERK1/2 pathways, SK-HEP1 and HepG2 cells were treated with 2 uM brivanib for 24 h and then stimulated with 40 ng/mL VEGF or bFGF. In addition, brivanib SK-HEP1 cells were also stimulated with IGF-1 for 15 min. The cells were lysed and the lysates were analyzed for levels of the effector proteins, including the serine/threonine kinase Akt and ERK1/2.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:15:22 GMT 2023
Edited
by admin
on Fri Dec 15 16:15:22 GMT 2023
Record UNII
DDU33B674I
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BRIVANIB
MI   USAN   WHO-DD  
USAN  
Official Name English
BRIVANIB [USAN]
Common Name English
BMS-540215
Code English
2-PROPANOL, 1-((4-((4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY)-5-METHYLPYRROLO(2,1-F)(1,2,4)TRIAZIN-6-YL)OXY)-, (2R)-
Systematic Name English
Brivanib [WHO-DD]
Common Name English
BRIVANIB [MI]
Common Name English
(2R)-1-({4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-ol
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
NCI_THESAURUS C1742
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C67040
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
PUBCHEM
11234052
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
ChEMBL
CHEMBL377300
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
MERCK INDEX
m2653
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY Merck Index
MESH
C509922
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
EPA CompTox
DTXSID60215294
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
CHEBI
167686
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
FDA UNII
DDU33B674I
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
SMS_ID
100000127529
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
DRUG BANK
DB11958
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
USAN
WW-39
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
EVMPD
SUB33565
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
CAS
649735-46-6
Created by admin on Fri Dec 15 16:15:22 GMT 2023 , Edited by admin on Fri Dec 15 16:15:22 GMT 2023
PRIMARY
Related Record Type Details
VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2
TARGET -> INHIBITOR
FIBROBLAST GROWTH FACTOR RECEPTOR 1
TARGET -> INHIBITOR
Related Record Type Details
Structure of 1H-INDOLE-2-CARBOXYLIC ACID, 4-FLUORO-5-((5-METHYL-6-((2R)-2-(SULFOOXY)PROPOXY)PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)OXY)-
METABOLITE -> PARENT
FECAL
Structure of 1H-INDOLE-2-CARBOXYLIC ACID, 4-FLUORO-5-((5-METHYL-6-((2R)-2-(SULFOOXY)PROPOXY)PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)OXY)-
METABOLITE -> PARENT
URINE
Structure of 1H-INDOLE-2-METHANOL, 4-FLUORO-5-((5-METHYL-6-((2R)-2-(SULFOOXY)PROPOXY)PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)OXY)-
METABOLITE -> PARENT
URINE
Structure of 2-PROPANOL, 1-((4-((4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY)-5-METHYLPYRROLO(2,1-F)(1,2,4)TRIAZIN-6-YL)OXY)-, 2-(HYDROGEN SULFATE), (2R)-
METABOLITE -> PARENT
PLASMA
Structure of PYRROLO(2,1-F)(1,2,4)TRIAZIN-6-OL, 4-((4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY)-5-METHYL-, 6-(HYDROGEN SULFATE)
METABOLITE -> PARENT
PLASMA
Structure of 4-FLUORO-5-(6-((2R)-2-HYDROXYPROPOXY)-5-METHYL-PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)OXY-1H-INDOLE-2-CARBOXYLIC ACID
METABOLITE -> PARENT
URINE
Structure of 4-FLUORO-5-(6-((2R)-2-HYDROXYPROPOXY)-5-METHYL-PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)OXY-1H-INDOLE-2-CARBOXYLIC ACID
METABOLITE -> PARENT
PLASMA
Structure of 1H-INDOLE-2-METHANOL, 4-FLUORO-5-((5-METHYL-6-((2R)-2-(SULFOOXY)PROPOXY)PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)OXY)-
METABOLITE -> PARENT
URINE
Structure of 4-FLUORO-5-(6-((2R)-2-HYDROXYPROPOXY)-5-METHYL-PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)OXY-1H-INDOLE-2-CARBOXYLIC ACID
METABOLITE -> PARENT
FECAL
Structure of 1H-INDOLE-2-CARBOXYLIC ACID, 4-FLUORO-5-((5-METHYL-6-(SULFOOXY)PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)OXY)-
METABOLITE -> PARENT
URINE
Structure of 2-PROPANOL, 1-((4-((4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY)-5-METHYLPYRROLO(2,1-F)(1,2,4)TRIAZIN-6-YL)OXY)-, 2-(HYDROGEN SULFATE), (2R)-
METABOLITE -> PARENT
FECAL
Structure of BRIVANIB ALANINATE
PRODRUG -> METABOLITE ACTIVE
Structure of 1H-INDOLE-2-CARBOXYLIC ACID, 4-FLUORO-5-((5-METHYL-6-(SULFOOXY)PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)OXY)-
METABOLITE -> PARENT
PLASMA
Related Record Type Details
Structure of BRIVANIB
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966