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
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
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 |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/17638901Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17638901
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16570908
Curator's Comment: # Bristol-Myers Squibb
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL5698 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29191878 |
3.0 nM [Kd] | ||
Target ID: CHEMBL5319 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29191878 |
1039.0 nM [Kd] | ||
Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29191878 |
1892.0 nM [Kd] | ||
Target ID: P35968 Gene ID: 3791.0 Gene Symbol: KDR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/18829493 |
25.0 nM [IC50] | ||
Target ID: P17948|||B3FR89 Gene ID: 2321.0 Gene Symbol: FLT1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17638901 |
0.38 µM [IC50] | ||
Target ID: P11362|||Q14307|||Q9UDF2 Gene ID: 2260.0 Gene Symbol: FGFR1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17638901 |
0.148 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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: 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: Page: p.1415 |
DLT: Mental status changes, Fatigue... Other AEs: Arterial hypertension... Dose limiting toxicities: Mental status changes (grade 3, 25%) Other AEs:Fatigue (grade 3, 25%) Arterial hypertension (grade 3-4, 25%) Sources: 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: 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: Page: p.1415 |
Other AEs: Dizziness, ALT increased... Other AEs: Dizziness (grade 3-4, 5%) Sources: Page: p.1415ALT 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%) |
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: 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: Page: p.3520-3522 |
Disc. AE: Cardio-respiratory arrest, Cerebral infarction... AEs leading to discontinuation/dose reduction: Cardio-respiratory arrest (grade 5, 0.17%) Sources: Page: p.3520-3522Cerebral 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%) |
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: 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: Page: p.137 |
Disc. AE: Dyspnoea, Cerebral haemorrhage... AEs leading to discontinuation/dose reduction: Dyspnoea (1.8%) Sources: Page: p.137Cerebral 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%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: Page: p.137 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/31633365/ |
likely | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/31633365/ |
likely | |||
minor [IC50 44.5 uM] | ||||
moderate [IC50 18.4 uM] | ||||
moderate [IC50 26.2 uM] | ||||
moderate [IC50 34.7 uM] | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/31633365/ |
weak | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/31633365/ |
weak | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/31633365/ |
weak | |||
yes [IC50 1.39 uM] | ||||
yes [IC50 25.3 uM] | ||||
yes [IC50 3.08 uM] | ||||
yes [IC50 3.64 uM] | ||||
yes [IC50 5.95 uM] | ||||
yes [IC50 6.98 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/31633365/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major [Km 32.7 uM] | ||||
major [Km 45 uM] | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
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 |
|
Comprehensive analysis of kinase inhibitor selectivity. | 2011 Oct 30 |
Patents
Sample Use Guides
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18829493
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
Edited
Fri Dec 15 15:56:19 GMT 2023
by
admin
on
Fri Dec 15 15:56:19 GMT 2023
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Record UNII |
U2Y5OFN795
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Record Status |
Validated (UNII)
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Record Version |
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-
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
336311
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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NCI_THESAURUS |
C1967
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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EU-Orphan Drug |
EU/3/11/918
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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NCI_THESAURUS |
C1742
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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Code System | Code | Type | Description | ||
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11154925
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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8879
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admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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U2Y5OFN795
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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C53397
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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SUB26391
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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SS-94
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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DTXSID20215295
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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DB11865
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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CHEMBL270995
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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m2653
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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100000089608
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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C509922
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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649735-63-7
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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167656
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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BRIVANIB ALANINATE
Created by
admin on Fri Dec 15 15:56:19 GMT 2023 , Edited by admin on Fri Dec 15 15:56:19 GMT 2023
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Related Record | Type | Details | ||
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METABOLITE ACTIVE -> PRODRUG |
Related Record | Type | Details | ||
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ACTIVE MOIETY |