Details
Stereochemistry | ACHIRAL |
Molecular Formula | C21H16ClF3N4O3 |
Molecular Weight | 464.825 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1
InChI
InChIKey=MLDQJTXFUGDVEO-UHFFFAOYSA-N
InChI=1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)
Molecular Formula | C21H16ClF3N4O3 |
Molecular Weight | 464.825 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/20812347
https://www.ncbi.nlm.nih.gov/pubmed/16757355
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/20812347
https://www.ncbi.nlm.nih.gov/pubmed/16757355
Sorafenib (BAY 43-9006), marketed as Nexavar by Bayer, is a drug approved for the treatment of advanced renal cell carcinoma (primary kidney cancer, hepatocellular carcinoma and for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine treatment. It has also received "Fast Track" designation by the FDA for the treatment of advanced hepatocellular carcinoma (primary liver cancer), and has since performed well in Phase III trials. Sorafenib was shown to interact with multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT- 3, VEGFR- 2, VEGFR- 3, and PDGFR- ß). Several of these kinases are thought to be involved in angiogenesis. Thus, sorafenib may inhibit tumor growth by a dual mechanism, acting either directly on the tumor (through inhibition of Raf and Kit signaling) and/or on tumor angiogenesis (through inhibition of VEGFR and PDGFR signaling). Sorafenib inhibited tumor growth of the murine renal cell carcinoma, RENCA, and several other human tumor xenografts in athymic mice. A reduction in tumor angiogenesis was seen in some tumor xenograft models.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=20470863
Curator's Comment: Sorafenib effectively crosses the blood-brain barrier and inhibits tumor growth in an orthotopic tumor model of glioblastoma
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL5145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20812347 |
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Target ID: CHEMBL1906 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20812347 |
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Target ID: CHEMBL2095227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16757355 |
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Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17229632 |
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Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17545544 |
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Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17545544 |
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Target ID: CHEMBL2041 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15466206 |
50.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | NEXAVAR Approved UseNEXAVAR is a kinase inhibitor indicated for the treatment of •Unresectable hepatocellular carcinoma (1.1) •Advanced renal cell carcinoma (1.2) •Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment (1.3) 1.1 Hepatocellular Carcinoma NEXAVAR® is indicated for the treatment of patients with unresectable hepatocellular carcinoma (HCC). 1.2 Renal Cell Carcinoma NEXAVAR is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). 1.3 Differentiated Thyroid Carcinoma NEXAVAR is indicated for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine treatment. Launch Date2005 |
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Primary | NEXAVAR Approved UseNEXAVAR is a kinase inhibitor indicated for the treatment of •Unresectable hepatocellular carcinoma (1.1) •Advanced renal cell carcinoma (1.2) •Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment (1.3) 1.1 Hepatocellular Carcinoma NEXAVAR® is indicated for the treatment of patients with unresectable hepatocellular carcinoma (HCC). 1.2 Renal Cell Carcinoma NEXAVAR is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). 1.3 Differentiated Thyroid Carcinoma NEXAVAR is indicated for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine treatment. Launch Date2005 |
|||
Primary | NEXAVAR Approved UseNEXAVAR is a kinase inhibitor indicated for the treatment of •Unresectable hepatocellular carcinoma (1.1) •Advanced renal cell carcinoma (1.2) •Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment (1.3) 1.1 Hepatocellular Carcinoma NEXAVAR® is indicated for the treatment of patients with unresectable hepatocellular carcinoma (HCC). 1.2 Renal Cell Carcinoma NEXAVAR is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). 1.3 Differentiated Thyroid Carcinoma NEXAVAR is indicated for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine treatment. Launch Date2005 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.35 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2.31 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9.81 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
7.21 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
800 mg 2 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2.44 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
3.42 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1.98 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
2.69 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
3.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22089297/ |
600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22089297/ |
400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.43 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18477034 |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
71.7 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
23.8 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
79 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
44.9 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
800 mg 2 times / day multiple, oral dose: 800 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
82.3 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
106.98 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
49.8 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
83.8 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
12.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22089297/ |
600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
17.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22089297/ |
400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9.4 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18477034 |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
28.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
23.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
37.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
28.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15613696/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
27.1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/18477034 |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.31% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22089297/ |
600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.29% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22089297/ |
400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SORAFENIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
DLT: Hypertension, Rash... Other AEs: Dyspnea, Rash... Dose limiting toxicities: Hypertension (grade 3, 33%) Other AEs:Rash (grade 2, 33%) Rash (grade 3, 67%) Dyspnea (grade 3, 33%) Sources: Rash (grade 3, 67%) Fatigue (grade 1, 67%) Anorexia (grade 1, 33%) Nausea (grade 1, 33%) Pharyngitis (grade 1, 33%) Dyspnea (grade 3, 33%) Pruritis (grade 1, 67%) |
600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Other AEs: Ascites, Constipation... Other AEs: Ascites (grade 3, 33%) Sources: Constipation (grade 3, 17%) Obstruction ureter (grade 3, 17%) Hypoalbuminemia (grade 3, 17%) Alkaline phosphatase (grade 3, 33%) Muscle weakness (grade 3, 17%) Depressed level of consciousness (grade 3, 17%) Pleural effusion (grade 3, 17%) Hypoxia (grade 3, 17%) Pruritis (grade 1, 17%) Rash (grade 1, 17%) Hypocalcemia (grade 1, 17%) |
800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Other AEs: Diarrhea... |
800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Other AEs: Hand and foot skin reaction, Desquamation... Other AEs: Hand and foot skin reaction (10%) Sources: Desquamation (5%) Fatigue (12.5%) Hypertension (5%) Mucositis oral (2.5%) Alopecia (12.5%) Dry skin (12.5%) Nausea (12.5%) Vomiting (12.5%) Anorexia (15%) Weight loss (17.5%) Hypocalcaemia (12.5%) |
400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Other AEs: Hypertension, Fatigue... Other AEs: Hypertension (grade 3, 2%) Sources: Fatigue (grade 3, 2%) Fever (grade 3, <1%) Weight loss (grade 3, <1%) Rash (grade 3, 1%) Hand and foot skin reaction (grade 3, 5%) Pruritus (grade 3, <1%) Flushing (grade 3, <1%) Diarrhea (grade 3, 2%) Nausea (grade 3, 1%) Anorexia (grade 3, 1%) Constipation (grade 3, 1%) Vomiting (grade 3, <1%) Mucositis (grade 3, <1%) Infection (grade 3, 1%) Cough (grade 3, <1%) Dyspnea (grade 3, 2%) Dyspnea (grade 4, <1%) Hypertension (grade 4, <1%) Fatigue (grade 4, <1%) Lymphopenia (grade 3, 5.1%) Amylase increased (grade 3, 2.4%) Hyperglycemia (grade 3, 4.1%) Hyperkalemia (grade 3, 2.1%) Lipase increased (grade 3, 3.5%) Hyponatremia (grade 3, 3.5%) Hypophosphatemia (grade 3, 1.8%) Lymphopenia (grade 4, 0.6%) Amylase increased (grade 4, 0.6%) Hyperglycemia (grade 4, 0.3%) Hyperkalemia (grade 4, 0.6%) Lipase increased (grade 4, 1.8%) |
100 mg 2 times / day multiple, oral Highest studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: |
unhealthy, Median age 60 years Health Status: unhealthy Age Group: Median age 60 years Sex: M+F Sources: |
DLT: Diarrhea... |
400 mg 2 times / day multiple, oral MTD Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 60 years Health Status: unhealthy Age Group: Median age 60 years Sex: M+F Sources: |
Disc. AE: Pancreatitis... AEs leading to discontinuation/dose reduction: Pancreatitis (grade 3, 6.7%) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Anorexia | grade 1, 33% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Nausea | grade 1, 33% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Pharyngitis | grade 1, 33% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Fatigue | grade 1, 67% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Pruritis | grade 1, 67% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Rash | grade 2, 33% DLT, Disc. AE |
800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Dyspnea | grade 3, 33% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Dyspnea | grade 3, 33% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Hypertension | grade 3, 33% DLT, Disc. AE |
800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Rash | grade 3, 67% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Rash | grade 3, 67% DLT, Disc. AE |
800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Hypocalcemia | grade 1, 17% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Pruritis | grade 1, 17% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Rash | grade 1, 17% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Constipation | grade 3, 17% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Depressed level of consciousness | grade 3, 17% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Hypoalbuminemia | grade 3, 17% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Hypoxia | grade 3, 17% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Muscle weakness | grade 3, 17% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Obstruction ureter | grade 3, 17% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Pleural effusion | grade 3, 17% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Alkaline phosphatase | grade 3, 33% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Ascites | grade 3, 33% | 600 mg 2 times / day multiple, oral MTD Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: |
Diarrhea | 22.5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Hand and foot skin reaction | 10% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Alopecia | 12.5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Dry skin | 12.5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Fatigue | 12.5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Hypocalcaemia | 12.5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Nausea | 12.5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Vomiting | 12.5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Anorexia | 15% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Weight loss | 17.5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Mucositis oral | 2.5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Desquamation | 5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Hypertension | 5% | 800 mg 2 times / day multiple, oral Highest studied dose Dose: 800 mg, 2 times / day Route: oral Route: multiple Dose: 800 mg, 2 times / day Sources: |
unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: |
Anorexia | grade 3, 1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Constipation | grade 3, 1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Infection | grade 3, 1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Nausea | grade 3, 1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Rash | grade 3, 1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Hypophosphatemia | grade 3, 1.8% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Diarrhea | grade 3, 2% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Dyspnea | grade 3, 2% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Fatigue | grade 3, 2% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Hypertension | grade 3, 2% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Hyperkalemia | grade 3, 2.1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Amylase increased | grade 3, 2.4% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Hyponatremia | grade 3, 3.5% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Lipase increased | grade 3, 3.5% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Hyperglycemia | grade 3, 4.1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Hand and foot skin reaction | grade 3, 5% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Lymphopenia | grade 3, 5.1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Cough | grade 3, <1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Fever | grade 3, <1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Flushing | grade 3, <1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Mucositis | grade 3, <1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Pruritus | grade 3, <1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Vomiting | grade 3, <1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Weight loss | grade 3, <1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Hyperglycemia | grade 4, 0.3% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Amylase increased | grade 4, 0.6% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Hyperkalemia | grade 4, 0.6% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Lymphopenia | grade 4, 0.6% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Lipase increased | grade 4, 1.8% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Dyspnea | grade 4, <1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Fatigue | grade 4, <1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Hypertension | grade 4, <1% | 400 mg 2 times / day multiple, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: |
Diarrhea | grade 3, 20% DLT |
100 mg 2 times / day multiple, oral Highest studied dose Dose: 100 mg, 2 times / day Route: oral Route: multiple Dose: 100 mg, 2 times / day Sources: |
unhealthy, Median age 60 years Health Status: unhealthy Age Group: Median age 60 years Sex: M+F Sources: |
Pancreatitis | grade 3, 6.7% Disc. AE |
400 mg 2 times / day multiple, oral MTD Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, Median age 60 years Health Status: unhealthy Age Group: Median age 60 years Sex: M+F Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
yes [IC50 0.84 uM] | ||||
yes [Ki 1.5 uM] | ||||
yes [Ki 1.5 uM] | ||||
yes [Ki 17 uM] | no (co-administration study) Comment: Administration of NEXAVAR 400 mg twice daily for 28 days did not alter the exposure of concomitantly administered midazolam (CYP3A4 substrate), dextromethorphan (CYP2D6 substrate), or omeprazole (CYP2C19 substrate). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf#page=45 Page: - |
|||
yes [Ki 2.4 uM] | ||||
yes [Ki 4.2 uM] | no (co-administration study) Comment: Administration of NEXAVAR 400 mg twice daily for 28 days did not alter the exposure of concomitantly administered midazolam (CYP3A4 substrate), dextromethorphan (CYP2D6 substrate), or omeprazole (CYP2C19 substrate). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf#page=45 Page: - |
|||
yes [Ki 4.9 uM] | no (co-administration study) Comment: Administration of NEXAVAR 400 mg twice daily for 28 days did not alter the exposure of concomitantly administered midazolam (CYP3A4 substrate), dextromethorphan (CYP2D6 substrate), or omeprazole (CYP2C19 substrate). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf#page=45 Page: - |
|||
yes [Ki 6.2 uM] | ||||
yes [Ki 7.3 uM] | no (co-administration study) Comment: The possible effect of sorafenib on a CYP2C9 substrate was assessed indirectly in patients receiving warfarin. The mean changes from baseline in PT-INR were not higher in NEXAVAR patients compared to placebo patients Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf#page=45 Page: - |
|||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | no (co-administration study) Comment: Ketoconazole (400 mg), a potent inhibitor of CYP3 A4, administered once daily for 7 days did not alter the mean AUC of a single oral 50 mg dose of sorafenib in healthy volunteers. There is no clinical information on the effect of CYP3A4 inducers on the pharmacokinetics of sorafenib. Substances that are inducers of CYP3A4 activity are expected to increase metabolism of sorafenib and thus decrease sorafenib concentrations. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=5 Page: - |
|||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes [Km 5.8 uM] | ||||
yes | ||||
yes | ||||
yes | unlikely Comment: The efflux ratio of sorafenib for transport from basolateral —> apical side to transport from the apical —> basolateral side of Caco-2 cells, ranged from 2.9 to 4.7. Given that sorafenib is highly permeable, the degree of efflux is not expected to result in an effect on overall absorption in man. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=47 Page: - |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
BAY 43-9006: early clinical data in patients with advanced solid malignancies. | 2002 |
|
Drug-drug interaction pharmacokinetic study with the Raf kinase inhibitor (RKI) BAY 43-9006 administered in combination with irinotecan (CPT-11) in patients with solid tumors. | 2003 Dec |
|
Antitumor effect and potentiation or reduction in cytotoxic drug activity in human colon carcinoma cells by the Raf kinase inhibitor (RKI) BAY 43-9006. | 2003 Dec |
|
Gateways to clinical trials. | 2004 Apr |
|
B-RAF is a therapeutic target in melanoma. | 2004 Aug 19 |
|
Use of mitogenic cascade blockers for treatment of C-Raf induced lung adenoma in vivo: CI-1040 strongly reduces growth and improves lung structure. | 2004 Jun 1 |
|
How thyroid tumors start and why it matters: kinase mutants as targets for solid cancer pharmacotherapy. | 2004 Nov |
|
Novel agents for the treatment of advanced kidney cancer. | 2004 Oct |
|
Validation of a liquid chromatography assay for the quantification of the Raf kinase inhibitor BAY 43-9006 in small volumes of mouse serum. | 2004 Sep 25 |
|
Improving outcomes in advanced malignant melanoma: update on systemic therapy. | 2005 |
|
Clinical trials referral resource. Current clinical trials of BAY 43-9006, Part 1. | 2005 Apr |
|
Raf kinase as a target for anticancer therapeutics. | 2005 Apr |
|
Subungual splinter hemorrhages: a clinical window to inhibition of vascular endothelial growth factor receptors? | 2005 Aug 16 |
|
Raf kinase inhibitors in oncology. | 2005 Feb |
|
The Raf kinase inhibitor BAY 43-9006 reduces cellular uptake of platinum compounds and cytotoxicity in human colorectal carcinoma cell lines. | 2005 Feb |
|
Multi-kinase inhibitors create buzz at ASCO. | 2005 Jun |
|
Novel kinase inhibitors in renal cell carcinoma: progressive development of static agents. | 2005 Mar |
|
Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors. | 2005 Mar 15 |
|
Angiogenesis and lung cancer: prognostic and therapeutic implications. | 2005 May 10 |
|
Update on angiogenesis inhibitors. | 2005 Nov |
|
Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. | 2005 Oct |
|
The role of Mcl-1 downregulation in the proapoptotic activity of the multikinase inhibitor BAY 43-9006. | 2005 Oct 20 |
|
Results of a phase I trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer. | 2005 Sep |
|
Spinal cord metastasis of a non-neurofibromatosis type-1 malignant peripheral nerve sheath tumor: an unusual manifestation of a rare tumor. | 2005 Sep |
|
Raf: a strategic target for therapeutic development against cancer. | 2005 Sep 20 |
|
Drug approval triggers debate on future direction for cancer treatments. | 2006 Feb |
|
Raf-1 kinase associates with Hepatitis C virus NS5A and regulates viral replication. | 2006 Jan 23 |
|
Targeting Raf-kinase: molecular rationales and translational issues. | 2006 Jun |
|
VEGF-targeted therapy in renal cell carcinoma: active drugs and active choices. | 2006 Mar |
|
Isolation and characterization of dominant and recessive IL-3-independent hematopoietic transformants. | 2006 Oct 26 |
Patents
Sample Use Guides
The recommended daily dose of NEXAVAR (tosylate salt of sorafenib) is 400 mg (2 x 200 mg tablets) taken twice daily, without food (at least 1 hour before or 2 hours after eating). Treatment should continue until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs.
432
433
434
435
436
437
438
439
Management of suspected adverse drug reactions may require temporary interruption and/or
dose reduction of NEXAVAR therapy. When dose reduction is necessary, the NEXAVAR
dose may be reduced to 400 mg once daily. If additional dose reduction is required,
NEXAVAR may be reduced to a single 400 mg dose every other day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=20470863
Patient-derived glioblastoma cells with low concentrations of sorafenib caused a dramatic dose dependent inhibition of proliferation (IC(50), 1.5 microM) and induction of apoptosis and autophagy. Sorafenib inhibited phosphorylation of signal transducer and activator of transcription 3 (Stat3) and expression of cyclins, D and E. In contrast, AKT was not modulated by sorafenib
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 21:24:38 GMT 2025
by
admin
on
Mon Mar 31 21:24:38 GMT 2025
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Record UNII |
9ZOQ3TZI87
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C129825
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WHO-VATC |
QL01XE05
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NCI_THESAURUS |
C1742
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WHO-ATC |
L01XE05
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NDF-RT |
N0000175076
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FDA ORPHAN DRUG |
675918
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FDA ORPHAN DRUG |
220206
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FDA ORPHAN DRUG |
185204
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EMA ASSESSMENT REPORTS |
NEXAVAR (AUTHORIZED: CARCINOMA, HEPATOCELLULAR, CARINOMA, RENAL CELL)
Created by
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FDA ORPHAN DRUG |
320310
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LIVERTOX |
NBK548944
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FDA ORPHAN DRUG |
229206
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NDF-RT |
N0000175605
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NCI_THESAURUS |
C1404
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8234
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495881
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Sorafenib
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C61948
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PRIMARY | |||
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C471405
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216239
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DTXSID7041128
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UU-02
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SORAFENIB
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CHEMBL1336
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8173
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5711
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DB00398
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2459
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9ZOQ3TZI87
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m10116
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PRIMARY | Merck Index | ||
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50924
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100000091433
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284461-73-0
Created by
admin on Mon Mar 31 21:24:38 GMT 2025 , Edited by admin on Mon Mar 31 21:24:38 GMT 2025
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PRIMARY | |||
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SUB23139
Created by
admin on Mon Mar 31 21:24:38 GMT 2025 , Edited by admin on Mon Mar 31 21:24:38 GMT 2025
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PRIMARY | |||
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9ZOQ3TZI87
Created by
admin on Mon Mar 31 21:24:38 GMT 2025 , Edited by admin on Mon Mar 31 21:24:38 GMT 2025
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PRIMARY |
Related Record | Type | Details | ||
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TARGET -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT | |||
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TARGET -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR |
IC50
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TARGET -> INHIBITOR | |||
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BINDER->LIGAND |
BINDING
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TARGET -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TARGET -> INHIBITOR |
IC50
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> SUBSTRATE |
Related Record | Type | Details | ||
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METABOLITE -> PARENT |
FECAL
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METABOLITE ACTIVE -> PARENT |
MAJOR
PLASMA
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METABOLITE -> PARENT |
PLASMA
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
FECAL
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METABOLITE -> PARENT |
PLASMA
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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