Details
Stereochemistry | ACHIRAL |
Molecular Formula | C22H18N4OS |
Molecular Weight | 386.47 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CNC(=O)C1=CC=CC=C1SC2=CC3=C(C=C2)C(\C=C\C4=CC=CC=N4)=NN3
InChI
InChIKey=RITAVMQDGBJQJZ-FMIVXFBMSA-N
InChI=1S/C22H18N4OS/c1-23-22(27)18-7-2-3-8-21(18)28-16-10-11-17-19(25-26-20(17)14-16)12-9-15-6-4-5-13-24-15/h2-14H,1H3,(H,23,27)(H,25,26)/b12-9+
Molecular Formula | C22H18N4OS |
Molecular Weight | 386.47 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.drugdevelopment-technology.com/projects/axitinib-carcinoma/; http://www.ncbi.nlm.nih.gov/pubmed/18541897; https://www.ncbi.nlm.nih.gov/pubmed/?term=19010843
Curator's Comment: description was created based on several sources, including
http://www.drugdevelopment-technology.com/projects/axitinib-carcinoma/; http://www.ncbi.nlm.nih.gov/pubmed/18541897; https://www.ncbi.nlm.nih.gov/pubmed/?term=19010843
Axitinib (trade name Inlyta) is a small molecule tyrosine kinase inhibitor developed by Pfizer. It has been shown to significantly inhibit growth of breast cancer in animal (xenograft) models and has shown partial responses in clinical trials with renal cell carcinoma (RCC) and several other tumour types. Axitinib has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. VEGF-mediated endothelial cell proliferation and survival were inhibited by axitinib in vitro and in mouse models. It was approved by the U.S. Food and Drug Administration.
CNS Activity
Sources: http://www.ncbi.nlm.nih.gov/pubmed/23729661
Curator's Comment: Mouse whole-body autoradiography revealed that [(14)C]axitinib-equivalents showed rapid absorption and distribution to all tissues except the brain. This suggests that efflux transport of axitinib may occur at the mouse blood-brain barrier
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P17948|||B3FR89 Gene ID: 2321.0 Gene Symbol: FLT1 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=19010843 |
0.1 nM [IC50] | ||
Target ID: P35968 Gene ID: 3791.0 Gene Symbol: KDR Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=19010843 |
0.2 nM [IC50] | ||
Target ID: P35916 Gene ID: 2324.0 Gene Symbol: FLT4 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=19010843 |
0.3 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Secondary | INLYTA Approved UseIndicated for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. Launch Date2012 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
32.2 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22644797 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
28.8 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22644797 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
52.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22644797 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
51.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19603168 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
162 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16027439 |
20 mg 2 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AXITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
27.8 ng/mL |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
82 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16027439 |
15 mg 1 times / day steady-state, oral dose: 15 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AXITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
27.8 ng/mL |
5 mg 2 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AXITINIB unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
160.3 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22644797 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
162 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22644797 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
206.8 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22644797 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
187 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19603168 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2171 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16027439 |
20 mg 2 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AXITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
265 ng × h/mL |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
717 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16027439 |
15 mg 1 times / day steady-state, oral dose: 15 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AXITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
265 ng × h/mL |
5 mg 2 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AXITINIB unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22644797 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
3 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22644797 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22644797 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB blood | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
9.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19603168 |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
4.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16027439 |
20 mg 2 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AXITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
4.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16027439 |
15 mg 1 times / day steady-state, oral dose: 15 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AXITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
AXITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
1% |
5 mg 2 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
AXITINIB unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED |
Doses
Dose | Population | Adverse events |
---|---|---|
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Disc. AE: Disease progression, Fatigue... AEs leading to discontinuation/dose reduction: Disease progression (11 patient) Sources: Fatigue (4 patients) Transient ischemic attack (3 patients) Asthenia (2 patients) Pleural effusion (2 patients) Decreased appetite (2 patients) Palmar-plantar erythrodysaesthesia syndrome (1 patient) Dyspnea (1 patient) Anemia (1 patient) Vomiting (1 patient) Retinal vein thrombosis (1 patient) Ascites (1 patient) Blood creatinine increased (1 patient) Hypoglycemia (1 patient) Altered state of consciousness (1 patient) Cerebral hemorrhage (1 patient) Dyspnea exertional (1 patient) Pneumothorax (1 patient) Hypertension (1 patient) |
30 mg 2 times / day steady, oral Highest studied dose Dose: 30 mg, 2 times / day Route: oral Route: steady Dose: 30 mg, 2 times / day Sources: |
unhealthy n = 2 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 2 Sources: |
|
5 mg 2 times / day steady, oral MTD Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy n = 8 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 8 Sources: |
DLT: Stomatitis... |
15 mg 1 times / day steady, oral Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: |
unhealthy n = 6 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 6 Sources: |
DLT: Hypertension, Stomatitis... Dose limiting toxicities: Hypertension (1 patient) Sources: Stomatitis (1 patient) Pancreatitis (1 patient) Bowel ischemia (1 patient) Thromboembolism (1 patient) |
20 mg 2 times / day steady, oral Dose: 20 mg, 2 times / day Route: oral Route: steady Dose: 20 mg, 2 times / day Sources: |
unhealthy n = 4 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 4 Sources: |
DLT: Hypertension, Hemoptysis... Dose limiting toxicities: Hypertension (2 patients) Sources: Hemoptysis (1 patient) Stomatitis (1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Altered state of consciousness | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Anemia | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Ascites | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Blood creatinine increased | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Cerebral hemorrhage | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Dyspnea exertional | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Dyspnea | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Hypertension | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Hypoglycemia | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Palmar-plantar erythrodysaesthesia syndrome | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Pneumothorax | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Retinal vein thrombosis | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Vomiting | 1 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Disease progression | 11 patient Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Asthenia | 2 patients Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Decreased appetite | 2 patients Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Pleural effusion | 2 patients Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Transient ischemic attack | 3 patients Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Fatigue | 4 patients Disc. AE |
5 mg 2 times / day steady, oral (starting) Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 20-82 years) n = 359 Health Status: unhealthy Age Group: 62 years (range: 20-82 years) Sex: M+F Population Size: 359 Sources: |
Stomatitis | 1 patient DLT |
5 mg 2 times / day steady, oral MTD Dose: 5 mg, 2 times / day Route: oral Route: steady Dose: 5 mg, 2 times / day Sources: |
unhealthy n = 8 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 8 Sources: |
Bowel ischemia | 1 patient DLT |
15 mg 1 times / day steady, oral Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: |
unhealthy n = 6 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 6 Sources: |
Hypertension | 1 patient DLT |
15 mg 1 times / day steady, oral Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: |
unhealthy n = 6 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 6 Sources: |
Pancreatitis | 1 patient DLT |
15 mg 1 times / day steady, oral Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: |
unhealthy n = 6 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 6 Sources: |
Stomatitis | 1 patient DLT |
15 mg 1 times / day steady, oral Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: |
unhealthy n = 6 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 6 Sources: |
Thromboembolism | 1 patient DLT |
15 mg 1 times / day steady, oral Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: |
unhealthy n = 6 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 6 Sources: |
Hemoptysis | 1 patient DLT |
20 mg 2 times / day steady, oral Dose: 20 mg, 2 times / day Route: oral Route: steady Dose: 20 mg, 2 times / day Sources: |
unhealthy n = 4 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 4 Sources: |
Stomatitis | 1 patient DLT |
20 mg 2 times / day steady, oral Dose: 20 mg, 2 times / day Route: oral Route: steady Dose: 20 mg, 2 times / day Sources: |
unhealthy n = 4 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 4 Sources: |
Hypertension | 2 patients DLT |
20 mg 2 times / day steady, oral Dose: 20 mg, 2 times / day Route: oral Route: steady Dose: 20 mg, 2 times / day Sources: |
unhealthy n = 4 Health Status: unhealthy Condition: advanced solid malignancies Population Size: 4 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes [IC50 4.5 uM] | ||||
yes [Ki 0.5 uM] | no (co-administration study) Comment: axitinib has no effect on exposure of paclitaxel |
|||
yes [Ki 0.7 uM] | ||||
yes [Ki 52.2 uM] | ||||
yes [Ki 8.3 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | yes (co-administration study) Comment: ketoconazole increased cmax of axitinib by by 50%, auc by 106% |
|||
major | yes (co-administration study) Comment: ketoconazole increased cmax of axitinib by by 50%, auc by 106% |
|||
minor | ||||
minor | no (pharmacogenomic study) Comment: no clinical effect was observed in genotyping study |
|||
minor | no (pharmacogenomic study) Comment: no clinical effect was observed in genotyping study |
|||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Modulation of the antitumor activity of metronomic cyclophosphamide by the angiogenesis inhibitor axitinib. | 2008 Jan |
|
Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. | 2009 Sep 20 |
|
Pharmacophore modeling and virtual screening studies for new VEGFR-2 kinase inhibitors. | 2010 Nov |
|
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 |
|
Evaluation of drugs with specific organ toxicities in organ-specific cell lines. | 2012 Mar |
|
The discovery of PLK4 inhibitors: (E)-3-((1H-Indazol-6-yl)methylene)indolin-2-ones as novel antiproliferative agents. | 2013 Aug 8 |
|
Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment. | 2015 Nov |
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=19010843
Transfected or endogenous RTK-expressing cells were treated by axitinib with range of concentration from 0.01 nM to 10 uM. In transfected or endogenous RTK-expressing cells, axitinib potently blocked growth factor-stimulated phosphorylation of VEGFR-2 and VEGFR-3 with average IC50 values of 0.2 and 0.1 to 0.3 nmol/L, respectively. Cellular activity against VEGFR-1 was 1.2 nmol/L.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 16:19:06 GMT 2023
by
admin
on
Fri Dec 15 16:19:06 GMT 2023
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Record UNII |
C9LVQ0YUXG
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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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WHO-ATC |
L01XE17
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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NCI_THESAURUS |
C1742
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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EMA ASSESSMENT REPORTS |
INLYTA (AUTHORIZED: CARCINOMA, CANCER CELL)
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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FDA ORPHAN DRUG |
730120
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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WHO-VATC |
QL01XE17
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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NCI_THESAURUS |
C93259
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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NDF-RT |
N0000175605
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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NCI_THESAURUS |
C129825
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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FDA ORPHAN DRUG |
230706
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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EU-Orphan Drug |
EU/3/10/844
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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LIVERTOX |
NBK548139
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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FDA ORPHAN DRUG |
240607
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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Code System | Code | Type | Description | ||
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4225
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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Axitinib
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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PRIMARY | |||
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1242999
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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PRIMARY | RxNorm | ||
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DTXSID3049049
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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C503983
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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PRIMARY | |||
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Axitinib
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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6450551
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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PRIMARY | |||
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m2153
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | Merck Index | ||
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C9LVQ0YUXG
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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100000089442
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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PRIMARY | |||
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SUB25427
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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CHEMBL1289926
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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N0000020000
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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PRIMARY | Receptor Tyrosine Kinase Inhibitors [MoA] | ||
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757441
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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PRIMARY | |||
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5659
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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RR-15
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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PRIMARY | |||
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8720
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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DB06626
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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C9LVQ0YUXG
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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66910
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY | |||
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C38718
Created by
admin on Fri Dec 15 16:19:07 GMT 2023 , Edited by admin on Fri Dec 15 16:19:07 GMT 2023
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PRIMARY | |||
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319460-85-0
Created by
admin on Fri Dec 15 16:19:06 GMT 2023 , Edited by admin on Fri Dec 15 16:19:06 GMT 2023
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PRIMARY |
Related Record | Type | Details | ||
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TARGET -> INHIBITOR | |||
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BINDER->LIGAND |
BINDING
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TARGET -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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TARGET -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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TARGET -> INHIBITOR |
Related Record | Type | Details | ||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
URINE
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METABOLITE INACTIVE -> PARENT |
MAJOR
PLASMA
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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