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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H24FN5O4
Molecular Weight 441.4555
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BRIVANIB ALANINATE

SMILES

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

InChI

InChIKey=LTEJRLHKIYCEOX-OCCSQVGLSA-N
InChI=1S/C22H24FN5O4/c1-11-7-15-16(27-11)5-6-17(19(15)23)32-21-20-13(3)18(8-28(20)26-10-25-21)30-9-12(2)31-22(29)14(4)24/h5-8,10,12,14,27H,9,24H2,1-4H3/t12-,14+/m1/s1

HIDE SMILES / InChI
Molecular Formula C22H24FN5O4
Molecular Weight 441.4555
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
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
144
Curator's Comment: # Bristol-Myers Squibb

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Vascular endothelial growth factor receptor 2
112
Target ID: P35968
Gene ID: 3791.0
Gene Symbol: KDR
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 25.0 nM [IC50]
Vascular endothelial growth factor receptor 1
44
Target ID: P17948|||B3FR89
Gene ID: 2321.0
Gene Symbol: FLT1
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 0.38 µM [IC50]
Fibroblast growth factor receptor 1
46
Target ID: P11362|||Q14307|||Q9UDF2
Gene ID: 2260.0
Gene Symbol: FGFR1
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 0.148 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
665
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
6146 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/20671097
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BRIVANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
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
45892 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/20671097
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BRIVANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
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
13.8 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/20671097
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BRIVANIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.3%
REVIEW
https://www.tandfonline.com/doi/full/10.1517/13543784.2011.565329
BRIVANIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
Other AEs: Fatigue, Arterial hypertension...
Other AEs:
Fatigue (grade 3-4, 15%)
Arterial hypertension (grade 3-4, 15%)
Diarrhea (grade 3-4, 10%)
Dizziness (grade 3-4, 5%)
ALT increased (grade 3-4, 15%)
AST increased (grade 3-4, 5%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
Disc. AE: Hepatic failure, Upper gastrointestinal hemorrhage...
AEs leading to
discontinuation/dose reduction:
Hepatic failure (grade 5, 0.17%)
Upper gastrointestinal hemorrhage (grade 5, 0.17%)
Cardio-respiratory arrest (grade 5, 0.17%)
Cerebral infarction (grade 5, 0.17%)
Diarrhea (grade 5, 0.17%)
Cerebrovascular accident (grade 5, 0.17%)
Asthenia (grade 5, 0.17%)
Gastrointestinal hemorrhage (grade 5, 0.17%)
Hematemesis (grade 5, 0.17%)
Fatigue (5%)
Hyponatremia (2%)
Decreased appetite (2%)
Hyperbilirubinemia (2%)
AST increased (2%)
Skin disorder (2%)
Skin disorder (3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Disc. AE: Vomiting, Dyspnoea...
AEs leading to
discontinuation/dose reduction:
Vomiting (1.8%)
Dyspnoea (1.8%)
Multi-organ failure (grade 5, 0.17%)
Cerebral haemorrhage (grade 5, 0.17%)
Hypovolemic shock (grade 5, 0.17%)
Intracranial haemorrhage (grade 5, 0.17%)
Bowel perforation (grade 5, 0.17%)
Pulmonary haemorrhage (grade 5, 0.17%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/21131369
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/23980084
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
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
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/31522033
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inducer
1087

substrate
1946

inhibitor
2252
substrate
1193

inhibitor
2438
inhibitor
2507

substrate
1388
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
MRP1
116

CYP2C8
1057

CYP3A5
136

CYP1A2
2153

CYP2B6
926

P-gp
1741

CYP2C19
2057

BCRP
910
CYP1A2
1197

SULTs
3

CYP1A1
389

CYP2C19
1119

P-gp
2052

SULT1A3
31

CYP1B1
104

BCRP
697

SULT2A1
28

CYP2C8
810

MRP1
113

SULT1A1
37

CYP2A6
626

SULT1E1
22

SULT1B1
8

CYP3A5
446

CYP2B6
776
CYP1A2
832

CYP2B6
669

P-gp
301

BCRP
101

MRP1
74
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2B6
1160
 likely
CYP3A4
2633
 likely
CYP1A2
2333
 minor [IC50 44.5 uM]
P-gp
1932
 moderate [IC50 18.4 uM]
CYP3A4
2633
 moderate [IC50 26.2 uM]
CYP2D6
2546
 moderate [IC50 34.7 uM]
CYP3A5
201
 no
BCRP
985
 weak
MRP1
232
 weak
P-gp
1932
 weak
CYP2C9
2497
 yes [IC50 1.39 uM]
MRP1
232
 yes [IC50 25.3 uM]
CYP2C8
1117
 yes [IC50 3.08 uM]
CYP2C19
2141
 yes [IC50 3.64 uM]
CYP2B6
1160
 yes [IC50 5.95 uM]
BCRP
985
 yes [IC50 6.98 uM]
CYP1A2
2333
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1946
 major [Km 32.7 uM]
CYP1A2
1197
 major [Km 45 uM]
CYP2A6
626
 minor
CYP2B6
776
 minor
CYP2C19
1119
 minor
CYP2C8
810
 minor
CYP2C9
1193
 minor
CYP2D6
1388
 minor
CYP3A5
446
 minor
SULT1A3
31
 minor
SULT2A1
28
 minor
BCRP
697
 no
MRP1
113
 no
P-gp
2052
 no
CYP1A1
389
 yes
CYP1B1
104
 yes
SULT1A1
37
 yes
SULT1B1
8
 yes
SULT1E1
22
 yes
SULTs
3
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
PubMed

PubMed

TitleDatePubMed
Discovery and validation of biomarkers that respond to treatment with brivanib alaninate, a small-molecule VEGFR-2/FGFR-1 antagonist.
2007 Jul 15
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 Mon Mar 31 18:13:51 GMT 2025
Edited
by admin
on Mon Mar 31 18:13:51 GMT 2025
Record UNII
U2Y5OFN795
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BRIVANIB ALANINATE
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
BMS-582664
Preferred Name English
BRIVANIB L-ALANINE ESTER [MI]
Common Name English
BRIVANIB ALANINATE [USAN]
Common Name English
BRIVANIB ALANINATE [JAN]
Common Name English
Brivanib alaninate [WHO-DD]
Common Name English
(1R)-2-[[4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxy]-1-methylethyl (2S)-2-aminopropanoate
Systematic Name English
BMS-582664-02
Code English
L-ALANINE, (1R)-2-((4-((4-FLUORO-2-METHYL-1H-INDOL-5-YL)OXY)-5-METHYLPYRROLO(2,1-F)(1,2,4)TRIAZIN-6-YL)OXY)-1-METHYLETHYL ESTER
Common Name English
brivanib alaninate [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 336311
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
NCI_THESAURUS C1967
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
EU-Orphan Drug EU/3/11/918
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
NCI_THESAURUS C1742
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
Code System Code Type Description
PUBCHEM
11154925
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
INN
8879
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
FDA UNII
U2Y5OFN795
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
NCI_THESAURUS
C53397
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
EVMPD
SUB26391
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
USAN
SS-94
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
EPA CompTox
DTXSID20215295
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
DRUG BANK
DB11865
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
ChEMBL
CHEMBL270995
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
MERCK INDEX
m2653
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY Merck Index
SMS_ID
100000089608
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
MESH
C509922
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
CAS
649735-63-7
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
CHEBI
167656
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
WIKIPEDIA
BRIVANIB ALANINATE
Created by admin on Mon Mar 31 18:13:51 GMT 2025 , Edited by admin on Mon Mar 31 18:13:51 GMT 2025
PRIMARY
Related Record Type Details
Structure of BRIVANIB
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
Structure of BRIVANIB
ACTIVE MOIETY
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