Identification

Name
Sorafenib
Accession Number
DB00398  (APRD01304, DB07438)
Type
Small Molecule
Groups
Approved, Investigational
Description

Sorafenib (rINN), marketed as Nexavar by Bayer, is a drug approved for the treatment of advanced renal cell carcinoma (primary kidney cancer). 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 is a small molecular inhibitor of Raf kinase, PDGF (platelet-derived growth factor), VEGF receptor 2 & 3 kinases and c Kit the receptor for Stem cell factor. A growing number of drugs target most of these pathways. The originality of Sorafenib lays in its simultaneous targeting of the Raf/Mek/Erk pathway.

Structure
Thumb
Synonyms
  • 4-(4-((((4-Chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-2-pyridinecarboxamide
  • N-(4-Chloro-3-(trifluoromethyl)phenyl)-n'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea
  • sorafenib
  • Sorafenibum
External IDs
BAY 43-9006 / BAY-43-9006
Product Ingredients
IngredientUNIICASInChI Key
Sorafenib Tosylate5T62Q3B36J475207-59-1IVDHYUQIDRJSTI-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NexavarTablet, film coated200 mg/1OralBayer Pharmaceuticals Corporartion2007-02-232007-02-23Us
NexavarTablet200 mgOralBayer2006-07-31Not applicableCanada
NexavarTablet, film coated200 mg/1OralBayer2005-12-20Not applicableUs50419 0488 58 nlmimage10 1c190e68
NexavarTablet, film coated200 mgOralBayer Pharma Ag2006-07-19Not applicableEu
Categories
UNII
9ZOQ3TZI87
CAS number
284461-73-0
Weight
Average: 464.825
Monoisotopic: 464.08630272
Chemical Formula
C21H16ClF3N4O3
InChI Key
MLDQJTXFUGDVEO-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide
SMILES
CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1

Pharmacology

Indication

Sorafenib is indicated for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma.

Associated Conditions
Pharmacodynamics

No large changes in QTc interval were observed. After one 28-day treatment cycle, the largest mean QTc interval change of 8.5 ms (upper bound of two-sided 90% confidence interval, 13.3 ms) was observed at 6 hours post-dose on day 1 of cycle 2.

Mechanism of action

Sorafenib interacts 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 reduces blood flow to the tumor. Sorafenib is unique in targeting the Raf/Mek/Erk pathway. By inhibiting these kinases, genetic transcription involving cell proliferation and angiogenesis is inhibited.

TargetActionsOrganism
ASerine/threonine-protein kinase B-raf
inhibitor
Human
ARAF proto-oncogene serine/threonine-protein kinase
inhibitor
Human
AVascular endothelial growth factor receptor 3
antagonist
Human
AVascular endothelial growth factor receptor 2
antagonist
Human
AReceptor-type tyrosine-protein kinase FLT3
antagonist
Human
APlatelet-derived growth factor receptor beta
antagonist
Human
AMast/stem cell growth factor receptor Kit
antagonist
Human
AFibroblast growth factor receptor 1
inhibitor
Human
AProto-oncogene tyrosine-protein kinase receptor Ret
inhibitor
Human
AVascular endothelial growth factor receptor 1
inhibitor
Human
Absorption

The mean relative bioavailability is 38-49% for the tablet form, when compared to an oral solution. Sorafenib reached peak plasma levels in 3 hours following oral administration. With a high-fat meal, bioavailability is reduced by 29% compared to administration in the fasted state.

Volume of distribution
Not Available
Protein binding

99.5% bound to plasma proteins.

Metabolism

Sorafenib is metabolized primarily in the liver, undergoing oxidative metabolism, mediated by CYP3A4, as well as glucuronidation mediated by UGT1A9. Sorafenib accounts for approximately 70-85% of the circulating analytes in plasma at steady- state. Eight metabolites of sorafenib have been identified, of which five have been detected in plasma. The main circulating metabolite of sorafenib in plasma, the pyridine N-oxide, shows in vitro potency similar to that of sorafenib. This metabolite comprises approximately 9-16% of circulating analytes at steady-state.

Route of elimination

Following oral administration of a 100 mg dose of a solution formulation of sorafenib, 96% of the dose was recovered within 14 days, with 77% of the dose excreted in feces, and 19% of the dose excreted in urine as glucuronidated metabolites.

Half life

25-48 hours

Clearance
Not Available
Toxicity

The highest dose of sorafenib studied clinically is 800 mg twice daily. The adverse reactions observed at this dose were primarily diarrhea and dermatologic events. No information is available on symptoms of acute overdose in animals because of the saturation of absorption in oral acute toxicity studies conducted in animals.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Sorafenib Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Sorafenib.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Sorafenib.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Sorafenib is combined with 2-Methoxyethanol.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Sorafenib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Sorafenib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Sorafenib.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Sorafenib.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Sorafenib.
5-FluorouridineThe risk or severity of QTc prolongation can be increased when Sorafenib is combined with 5-Fluorouridine.
6-Deoxyerythronolide BThe metabolism of Sorafenib can be decreased when combined with 6-Deoxyerythronolide B.
Food Interactions
Not Available

References

Synthesis Reference

Ales Gavenda, Alexandr Jegorov, Pierluigi Rossetto, Peter Lindsay MacDonald, Augusto Canavesi, "POLYMORPHS OF SORAFENIB TOSYLATE AND SORAFENIB HEMI-TOSYLATE, AND PROCESSES FOR PREPARATION THEREOF." U.S. Patent US20090192200, issued July 30, 2009.

US20090192200
General References
Not Available
External Links
Human Metabolome Database
HMDB0014542
KEGG Drug
D08524
PubChem Compound
216239
PubChem Substance
46505329
ChemSpider
187440
BindingDB
16673
ChEBI
50924
ChEMBL
CHEMBL1336
Therapeutic Targets Database
DAP000006
PharmGKB
PA7000
HET
BAX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sorafenib
ATC Codes
L01XE05 — Sorafenib
AHFS Codes
  • 92:00.00 — Miscellaneous Therapeutic Agents
PDB Entries
1uwh / 1uwj / 3gcs / 3heg / 3rgf / 3wze / 4asd / 5hi2
FDA label
Download (310 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentRenal Cancers1
0TerminatedTreatmentHepatocellular,Carcinoma1
1Active Not RecruitingTreatmentAdult Primary Hepatocellular Carcinoma / Advanced Adult Hepatocellular Carcinoma / Advanced Adult Primary Liver Cancer / BCLC Stage B Adult Hepatocellular Carcinoma / BCLC Stage C Adult Hepatocellular Carcinoma1
1Active Not RecruitingTreatmentAdult Solid Neoplasm / Advanced Malignant Solid Neoplasm / Recurrent Melanoma / Refractory Malignant Solid Neoplasm / Stage III Cutaneous Melanoma AJCC v7 / Stage IIIA Cutaneous Melanoma AJCC v7 / Stage IIIA Skin Melanoma / Stage IIIB Cutaneous Melanoma AJCC v7 / Stage IIIB Skin Melanoma / Stage IIIC Cutaneous Melanoma AJCC v7 / Stage IIIC Skin Melanoma / Stage IV Cutaneous Melanoma AJCC v6 and v7 / Stage IV Skin Melanoma / Stages III Skin Melanoma1
1Active Not RecruitingTreatmentAdvanced Cancers / Advanced Malignant Neoplasm / BRAF Gene Mutation / Metastatic Malignant Neoplasm / Recurrent Malignant Neoplasm / Refractory Malignant Neoplasm1
1Active Not RecruitingTreatmentCancer, Advanced2
1Active Not RecruitingTreatmentCancer, Advanced / Tumors, Solid1
1Active Not RecruitingTreatmentHepatocellular,Carcinoma2
1Active Not RecruitingTreatmentHepatocellular,Carcinoma / Malignant Neoplasm of Pancreas1
1Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Therapy-Related Acute Myeloid Leukemia / Untreated Adult Acute Myeloid Leukemia1
1Active Not RecruitingTreatmentLiver Cancer1
1Active Not RecruitingTreatmentLiver Cancer / Renal Cancers1
1Active Not RecruitingTreatmentMetastatic Renal Cell Carcinoma1
1Active Not RecruitingTreatmentNeuroblastomas1
1Active Not RecruitingTreatmentNon Small Cell Lung Carcinoma (NSCLC)1
1Active Not RecruitingTreatmentTumors Metastatic to Brain1
1Active Not RecruitingTreatmentTumors, Solid1
1CompletedNot AvailableAdvanced Solid Tumors / Refractory to Standard Therapies1
1CompletedNot AvailableDrug Drug Interaction (DDI)1
1CompletedNot AvailableNeoplasms1
1CompletedBasic ScienceKidney Diseases1
1CompletedBasic ScienceLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
1CompletedHealth Services ResearchFasting1
1CompletedOtherBiological Availability1
1CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Leukemias1
1CompletedTreatmentAcute Promyelocytic Leukemia (APL) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
1CompletedTreatmentAdenocarcinoma of the Pancreas / Malignant Neoplasm of Pancreas1
1CompletedTreatmentAdult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia1
1CompletedTreatmentAdult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult Acute Megakaryoblastic Leukemia / Adult Acute Monoblastic Leukemia / Adult Acute Monocytic Leukemia / Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With Maturation / Adult Acute Myeloid Leukemia With Minimal Differentiation / Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 / Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1 / Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL / Adult Acute Myeloid Leukemia Without Maturation / Adult Acute Myelomonocytic Leukemia / Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA / Adult Erythroleukemia / Adult Pure Erythroid Leukemia / Alkylating Agent-Related Acute Myeloid Leukemia / Blastic Phase / De Novo Myelodysplastic Syndrome / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Secondary Myelodysplastic Syndromes1
1CompletedTreatmentAdult Anaplastic Astrocytoma / Adult Anaplastic Oligodendroglioma / Adult Giant Cell Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Tumor1
1CompletedTreatmentAdult Hepatocellular Carcinoma / Advanced Adult Hepatocellular Carcinoma / Localized Non-Resectable Adult Liver Carcinoma / Recurrent Adult Liver Carcinoma1
1CompletedTreatmentAdult Primary Hepatocellular Carcinoma / Advanced Adult Primary Liver Cancer / Localized Resectable Adult Primary Liver Cancer / Localized Unresectable Adult Primary Liver Cancer / Recurrent Adult Primary Liver Cancer1
1CompletedTreatmentAdvanced Cancers1
1CompletedTreatmentAdvanced Malignant Neoplasm1
1CompletedTreatmentAdvanced Solid Tumors3
1CompletedTreatmentAdvanced Solid Tumors / Malignant Lymphomas1
1CompletedTreatmentBiphenotypic Leukemia / Infantile Leukemia (Both AML and ALL) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Myelodysplastic/Myeloproliferative Neoplasms1
1CompletedTreatmentBladder Cancers1
1CompletedTreatmentBladder Cancers / Renal Pelvis Cancer / Transitional Cell Carcinoma / Ureteral Cancer / Urethral Cancer1
1CompletedTreatmentCancer, Breast / Colorectal Cancers / Head and Neck Carcinoma / Lung Cancers / Malignant Neoplasm of Pancreas / Mesothelioma / Prostate Cancer / Sarcomas1
1CompletedTreatmentCarcinoid Tumors / Neuroendocrine Tumors / Progressive Neuroendocrine Tumors of pancreatic origin1
1CompletedTreatmentCarcinoma NOS1
1CompletedTreatmentCarcinoma, Small Cell / Lung Cancers1
1CompletedTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Refractory Multiple Myeloma / Stage III Multiple Myeloma / Stage IV Chronic Lymphocytic Leukemia / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentEwing's Sarcoma Family of Tumors / Neoplasms, Brain / Neuroblastomas / Rhabdomyosarcoma and Other Soft Tissue Sarcomas / Sarcoma, Osteogenic1
1CompletedTreatmentExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Small Lymphocytic Lymphoma / Refractory Multiple Myeloma / Splenic Marginal Zone Lymphoma / Stage II Multiple Myeloma / Stage III Adult Burkitt Lymphoma / Stage III Adult Diffuse Large Cell Lymphoma / Stage III Adult Diffuse Mixed Cell Lymphoma / Stage III Adult Diffuse Small Cleaved Cell Lymphoma / Stage III Adult Immunoblastic Large Cell Lymphoma / Stage III Adult Lymphoblastic Lymphoma / Stage III Grade 1 Follicular Lymphoma / Stage III Grade 2 Follicular Lymphoma / Stage III Grade 3 Follicular Lymphoma / Stage III Mantle Cell Lymphoma / Stage III Marginal Zone Lymphoma / Stage III Multiple Myeloma / Stage III Small Lymphocytic Lymphoma / Stage IV Adult Burkitt Lymphoma / Stage IV Adult Diffuse Large Cell Lymphoma / Stage IV Adult Diffuse Mixed Cell Lymphoma / Stage IV Adult Diffuse Small Cleaved Cell Lymphoma / Stage IV Adult Immunoblastic Large Cell Lymphoma / Stage IV Adult Lymphoblastic Lymphoma / Stage IV Grade 1 Follicular Lymphoma / Stage IV Grade 2 Follicular Lymphoma / Stage IV Grade 3 Follicular Lymphoma / Stage IV Mantle Cell Lymphoma / Stage IV Marginal Zone Lymphoma / Stage IV Small Lymphocytic Lymphoma / Unspecified Adult Solid Tumor, Protocol Specific / Waldenström's Macroglobulinemia (WM)1
1CompletedTreatmentGastrointestinal Tumors / Metastatic Breast Cancer (MBC)1
1CompletedTreatmentGlioblastomas / Gliosarcoma1
1CompletedTreatmentHepatocellular Cancer1
1CompletedTreatmentHepatocellular Cancer / Liver Cancer1
1CompletedTreatmentHepatocellular,Carcinoma10
1CompletedTreatmentHepatocellular,Carcinoma / Liver Cancer / Localized Unresectable Liver Cancer1
1CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)2
1CompletedTreatmentLeukemias / Refractory Solid Tumors1
1CompletedTreatmentLiver Cancer1
1CompletedTreatmentLiver Diseases1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Relapsed and/or Refractory Solid Tumors / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentLung Cancers1
1CompletedTreatmentMalignancies2
1CompletedTreatmentMalignant Neoplasm of Pancreas1
1CompletedTreatmentMalignant Neoplasm of Stomach1
1CompletedTreatmentMalignant Solid Tumours / Non Small Cell Lung Carcinoma (NSCLC) / Renal Cell Adenocarcinoma1
1CompletedTreatmentMelanoma1
1CompletedTreatmentMelanoma (Skin)1
1CompletedTreatmentMelanoma / Recurrent Melanoma / Stage III Melanoma / Stage IV Melanoma1
1CompletedTreatmentMelanoma / Renal Cancers1
1CompletedTreatmentMetastatic Brain Tumors / Primary Brain Tumors1
1CompletedTreatmentMetastatic Colon Cancer / Recurrent Colon Cancer / Recurrent Rectal Cancer / Stage III Colon Cancer / Stage III Rectal Cancer / Stage IV Rectal Cancer1
1CompletedTreatmentMetastatic Colorectal Cancers1
1CompletedTreatmentMetastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma / Recurrent Metastatic Squamous Neck Cancer With Occult Primary / Recurrent Salivary Gland Cancer / Recurrent Squamous Cell Carcinoma of the Hypopharynx / Recurrent Squamous Cell Carcinoma of the Larynx / Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity / Recurrent Squamous Cell Carcinoma of the Nasopharynx / Recurrent Squamous Cell Carcinoma of the Oropharynx / Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Recurrent Verrucous Carcinoma of the Larynx / Recurrent Verrucous Carcinoma of the Oral Cavity / Salivary Gland Squamous Cell Carcinoma / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Nasopharynx / Stage IVA Oral Cavity Squamous Cell Carcinoma / Stage IVA Salivary Gland Cancer / Stage IVA Squamous Cell Carcinoma of the Larynx / Stage IVA Squamous Cell Carcinoma of the Oropharynx / Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVA Verrucous Carcinoma of the Larynx / Stage IVA Verrucous Carcinoma of the Oral Cavity / Stage IVB Salivary Gland Cancer / Stage IVB Squamous Cell Carcinoma of the Larynx / Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVB Squamous Cell Carcinoma of the Oropharynx / Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVB Verrucous Carcinoma of the Larynx / Stage IVB Verrucous Carcinoma of the Oral Cavity / Stage IVC Salivary Gland Cancer / Stage IVC Squamous Cell Carcinoma of the Larynx / Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVC Squamous Cell Carcinoma of the Oropharynx / Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVC Verrucous Carcinoma of the Larynx / Stage IVC Verrucous Carcinoma of the Oral Cavity / Tongue Cancer / Untreated Metastatic Squamous Neck Cancer With Occult Primary1
1CompletedTreatmentNeoplasms5
1CompletedTreatmentOcular Melanoma1
1CompletedTreatmentPrimary Disease / Prostate Cancer1
1CompletedTreatmentProstate Cancer1
1CompletedTreatmentPulmonary Arterial Hypertension (PAH)1
1CompletedTreatmentRectal Carcinoma1
1CompletedTreatmentRecurrent Colon Carcinoma / Recurrent Rectal Carcinoma / Stage IVA Colon Cancer / Stage IVA Rectal Cancer / Stage IVB Colon Cancer / Stage IVB Rectal Cancer1
1CompletedTreatmentRefractory Malignancy1
1CompletedTreatmentRefractory Solid Tumors1
1CompletedTreatmentRenal Cancers / Tumors1
1CompletedTreatmentRenal Cell Adenocarcinoma1
1CompletedTreatmentSarcomas1
1CompletedTreatmentT Cell Lymphomas1
1CompletedTreatmentTumors, Solid3
1CompletedTreatmentUnresectable or Metastatic Hepatocellular Carcinoma (HCC)1
1CompletedTreatmentUnspecified Adult Solid Tumor1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific4
1Not Yet RecruitingTreatmentHealthy, Male1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Hematopoietic/Lymphoid Cancer / Leukemia Acute Myeloid Leukemia (AML)1
1RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Untreated Adult Acute Myeloid Leukemia1
1RecruitingTreatmentAdenocarcinoma of the Pancreas / Recurrent Pancreatic Carcinoma / Stage IA Pancreatic Cancer / Stage IB Pancreatic Cancer / Stage IIA Pancreatic Cancer / Stage IIB Pancreatic Cancer / Stage III Pancreatic Cancer1
1RecruitingTreatmentAdvanced Solid Tumors / Hepatocellular,Carcinoma1
1RecruitingTreatmentCancer, Breast / Metastatic Brain Tumors1
1RecruitingTreatmentChild-Pugh Class A / Child-Pugh Class B / Hepatitis B Infection / Hepatitis C Infection / Liver Cirrhosis / Metastatic Malignant Solid Neoplasm / Recurrent Hepatocellular Carcinoma / Recurrent Malignant Solid Neoplasm / Refractory Malignant Neoplasm / Solid Neoplasms / Stage IV Hepatocellular Carcinoma / Stage IV Hepatocellular Carcinoma AJCC v7 / Unresectable Solid Neoplasm1
1RecruitingTreatmentHepatocellular Cancer / Liver Cancer1
1RecruitingTreatmentHepatocellular,Carcinoma1
1TerminatedBasic ScienceRenal Cell Adenocarcinoma1
1TerminatedTreatmentAdult Acute Basophilic Leukemia / Adult Acute Eosinophilic Leukemia / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Blastic Phase Chronic Myelogenous Leukemia / Recurrent Adult Acute Myeloid Leukemia / Unspecified Adult Solid Tumor, Protocol Specific1
1TerminatedTreatmentHHV-8 / Kaposi s Sarcoma (KS) / KSHV1
1TerminatedTreatmentHepatocellular,Carcinoma3
1TerminatedTreatmentLiver Cancer2
1TerminatedTreatmentLung Cancers1
1TerminatedTreatmentMetastatic Colorectal Cancers1
1TerminatedTreatmentNeoplasms1
1TerminatedTreatmentRenal Cancers1
1TerminatedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1Unknown StatusTreatmentHepatocellular,Carcinoma1
1Unknown StatusTreatmentMetastatic or Locally Advanced Solid Tumors1
1WithdrawnNot AvailableLocally Advanced Squamous Cell Carcinomas of the Head and Neck (SCCHN)1
1WithdrawnTreatmentAdvanced Cancers1
1WithdrawnTreatmentHepatocellular Cancer1
1WithdrawnTreatmentHepatocellular Cancer / Hepatocellular,Carcinoma / Liver Cancer1
1WithdrawnTreatmentHepatocellular,Carcinoma1
1WithdrawnTreatmentHepatocellular,Carcinoma / Liver Cancer / Unresectable Hepatocellular Carcinoma1
1, 2Active Not RecruitingTreatmentHCC / Hepatocellular,Carcinoma / Liver Cancer1
1, 2Active Not RecruitingTreatmentHepatocellular,Carcinoma4
1, 2Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Leukemias1
1, 2Active Not RecruitingTreatmentLiver Metastasis / Malignancies1
1, 2Active Not RecruitingTreatmentMalignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm1
1, 2Active Not RecruitingTreatmentMetastatic Breast Cancer (MBC)1
1, 2CompletedNot AvailableRenal Cell Adenocarcinoma1
1, 2CompletedTreatmentAcinar Cell Adenocarcinoma of the Pancreas / Duct Cell Adenocarcinoma of the Pancreas / Recurrent Pancreatic Cancer / Stage IV Pancreatic Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
1, 2CompletedTreatmentAdenoma, Liver Cell / Hepatocellular,Carcinoma / Liver Neoplasms, Experimental / Neoplasms, Hepatic1
1, 2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Neoplasm / Recurrent Adult Brain Tumor1
1, 2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Tumor1
1, 2CompletedTreatmentAdvanced Gastric Cancer1
1, 2CompletedTreatmentAdvanced Hepatocellular Carcinoma1
1, 2CompletedTreatmentAdvanced Liver Cancer / Metastatic Hepatocellular Carcinoma1
1, 2CompletedTreatmentBile Duct Neoplasms / Neoplasms, Pancreatic1
1, 2CompletedTreatmentCancer of the Cervix1
1, 2CompletedTreatmentCancer, Advanced1
1, 2CompletedTreatmentCancer, Breast1
1, 2CompletedTreatmentChromophobe Renal Cell Carcinoma / Clear Cell Renal Cell Carcinoma / Papillary Renal Cell Carcinoma / Renal Cell Carcinoma Recurrent / Sarcomatoid Renal Cell Carcinoma / Stage IV Renal Cell Cancer1
1, 2CompletedTreatmentColorectal Cancers1
1, 2CompletedTreatmentHepatocellular,Carcinoma4
1, 2CompletedTreatmentHepatocellular,Carcinoma / Liver Cancer1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Disorders1
1, 2CompletedTreatmentLeukemias1
1, 2CompletedTreatmentLeukemias / With AML and FLT3-ITD Mutations1
1, 2CompletedTreatmentLiver Cancer1
1, 2CompletedTreatmentMetastatic Breast Cancer (MBC)1
1, 2CompletedTreatmentMetastatic Colorectal Cancers1
1, 2CompletedTreatmentMultiple Myeloma (MM)1
1, 2CompletedTreatmentProstate Cancer1
1, 2CompletedTreatmentRecurrent Breast Cancer / Stage IV Breast Cancer1
1, 2CompletedTreatmentRenal Cancers1
1, 2CompletedTreatmentRenal Cell Adenocarcinoma2
1, 2CompletedTreatmentRenal Cell Carcinoma Recurrent / Stage III Renal Cell Cancer / Stage III Renal Cell Cancer AJCC v7 / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V71
1, 2CompletedTreatmentSoft Tissue Sarcoma (STS)1
1, 2CompletedTreatmentSquamous Cell Cancer1
1, 2RecruitingTreatmentAcute Biphenotypic Leukemia (ABL) / De Novo Myelodysplastic Syndrome / High Risk Myelodysplastic Syndrome / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Myeloproliferative Neoplasms1
1, 2RecruitingTreatmentAdvanced Adult Hepatocellular Carcinoma / Child-Pugh Class A / Stage III Hepatocellular Carcinoma / Stage IIIA Hepatocellular Carcinoma / Stage IIIB Hepatocellular Carcinoma / Stage IIIC Hepatocellular Carcinoma / Stage IV Hepatocellular Carcinoma / Stage IVA Hepatocellular Carcinoma / Stage IVB Hepatocellular Carcinoma1
1, 2RecruitingTreatmentAnaplastic Gliomas / Glioblastomas / Neoplasms, Brain1
1, 2RecruitingTreatmentHepatocellular Carcinoma Non-resectable / Recurrent Hepatocellular Carcinoma1
1, 2RecruitingTreatmentHepatocellular,Carcinoma2
1, 2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic1
1, 2SuspendedTreatmentAdvanced Solid Tumors1
1, 2TerminatedTreatmentBiliary Tract Cancer / Cholangiocarcinomas / Gallbladder Cancer1
1, 2TerminatedTreatmentCancer of the Ovary1
1, 2TerminatedTreatmentHepatocellular,Carcinoma3
1, 2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2
1, 2TerminatedTreatmentLung Cancers1
1, 2TerminatedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
1, 2TerminatedTreatmentProstate Cancer1
1, 2Unknown StatusTreatmentHepatocellular,Carcinoma1
1, 2Unknown StatusTreatmentMelanoma (Skin)2
1, 2Unknown StatusTreatmentMetastatic Breast Cancer (MBC)1
1, 2Unknown StatusTreatmentSoft Tissue Sarcoma (STS)1
1, 2WithdrawnTreatmentAdvanced Hepatocellular Carcinoma1
1, 2WithdrawnTreatmentHepatocellular,Carcinoma1
2Active Not RecruitingTreatmentAcute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13.3;q13.1); RBM15-MKL1 / Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13.3;q13.3); RBM15-MKL1 / Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13;q13); RBM15-MKL1 / Acute Myeloid Leukemia With a Variant RARA Translocation / Acute Myeloid Leukemia With Inv(3) (q21.3;q26.2) or t(3;3) (q21.3;q26.2); GATA2, MECOM / Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1 / Acute Myeloid Leukemia With t(6;9) (p23;q34.1); DEK-NUP214 / Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214 / Acute Myeloid Leukemia With t(9;11)(p21.3;q23.3); MLLT3-KMT2A / Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A / Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL / Acute Myeloid Leukemia With Variant MLL Translocations / Leukemia Acute Myeloid Leukemia (AML) / Untreated Adult Acute Myeloid Leukemia1
2Active Not RecruitingTreatmentAdult Primary Hepatocellular Carcinoma / Localized Resectable Adult Primary Liver Cancer / Localized Unresectable Adult Primary Liver Cancer / Recurrent Adult Primary Liver Cancer1
2Active Not RecruitingTreatmentCHILD B / Hepatocellular,Carcinoma1
2Active Not RecruitingTreatmentCancer, Breast2
2Active Not RecruitingTreatmentClear Cell Renal Cell Carcinoma / Renal Cell Cancer, Recurrent / Renal Cell Carcinoma Recurrent / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V71
2Active Not RecruitingTreatmentDesmoplastic Small Round Cell Tumor (DSRCT) / Ewing Sarcoma of Bone or Soft Tissue / Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor1
2Active Not RecruitingTreatmentDifferentiated Thyroid Cancer (DTC)1
2Active Not RecruitingTreatmentGastrointestinal Stromal Tumors1
2Active Not RecruitingTreatmentHCC1
2Active Not RecruitingTreatmentHead and Neck Carcinoma / Metastatic Head and Neck Squamous Cell Carcinoma / Metastatic Squamous Cell Carcinoma of the Hypopharynx / Metastatic Squamous Cell Carcinoma of the Larynx / Metastatic Squamous Cell Carcinoma of the Oral Cavity / Metastatic Squamous Cell Carcinoma of the Oropharynx / Recurrent Head and Neck Squamous Cell Carcinoma / Recurrent Hypopharyngeal Squamous Cell Carcinoma / Recurrent Laryngeal Squamous Cell Carcinoma / Recurrent Oral Cavity Squamous Cell Carcinoma / Recurrent Oropharyngeal Squamous Cell Carcinoma / Squamous Cell Carcinoma (SCC)1
2Active Not RecruitingTreatmentHepatocellular Cancer2
2Active Not RecruitingTreatmentHepatocellular,Carcinoma4
2Active Not RecruitingTreatmentHepatocellular,Carcinoma / Metastasis1
2Active Not RecruitingTreatmentHepatocellular,Carcinoma / Secondary1
2Active Not RecruitingTreatmentLeukemias1
2Active Not RecruitingTreatmentLiver Cancer2
2Active Not RecruitingTreatmentLung Cancers1
2Active Not RecruitingTreatmentMetastatic Colon Cancer / Recurrent Colon Cancer / Recurrent Rectal Cancer / Stage IV Rectal Cancer1
2Active Not RecruitingTreatmentMultiple Endocrine Neoplasia / Recurrent Thyroid Gland Carcinoma / Thyroid Gland Medullary Carcinoma1
2Active Not RecruitingTreatmentPleomorphic Rhabdomyosarcoma / Stage IIB Adult Soft Tissue Sarcoma / Stage IIB Adult Soft Tissue Sarcoma AJCC v7 / Stage III Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma AJCC v7 / Stage IV Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma AJCC v71
2Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
2Active Not RecruitingTreatmentRenal Cell Carcinoma Recurrent / Stage III Renal Cell Cancer / Stage III Renal Cell Cancer AJCC v7 / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V71
2Active Not RecruitingTreatmentUveal Melanoma1
2CompletedSupportive CareNeuroendocrine Tumors1
2CompletedTreatmentAdenocarcinoma of the Extrahepatic Bile Duct / Adenocarcinoma of the Gallbladder / Adenocarcinoma With Squamous Metaplasia of the Gallbladder / Cholangiocarcinoma of the Extrahepatic Bile Duct / Cholangiocarcinoma of the Gallbladder / Recurrent Extrahepatic Bile Duct Cancer / Recurrent Gallbladder Cancer / Squamous Cell Carcinoma of the Gallbladder / Unresectable Extrahepatic Bile Duct Cancer / Unresectable Gallbladder Cancer1
2CompletedTreatmentAdenocarcinoma of Colon / Adenocarcinoma of Rectum / Metastatic Disease1
2CompletedTreatmentAdenocarcinoma of the Pancreas / Recurrent Pancreatic Cancer / Stage II Pancreatic Cancer / Stage III Pancreatic Cancer / Stage IV Pancreatic Cancer1
2CompletedTreatmentAdenocarcinoma of the Prostate1
2CompletedTreatmentAdenocarcinoma of the Prostate / Stage II Prostate Cancer / Stage III Prostate Cancer1
2CompletedTreatmentAdenocarcinomas1
2CompletedTreatmentAdenocarcinomas of the Gastroesophageal Junction / Advanced Unresectable Gastric Cancer / Metastatic Gastric Cancers1
2CompletedTreatmentAdult Angiosarcoma / Adult Epithelioid Sarcoma / Adult Leiomyosarcoma / Adult Malignant Fibrous Histiocytoma / Adult Neurofibrosarcoma / Adult Synovial Sarcoma / Ovarian Sarcoma / Recurrent Adult Soft Tissue Sarcoma / Recurrent Uterine Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage III Uterine Sarcoma / Stage IV Adult Soft Tissue Sarcoma / Stage IV Uterine Sarcoma / Uterine Carcinosarcoma / Uterine Leiomyosarcoma1
2CompletedTreatmentAdult Giant Cell Glioblastoma / Adult Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Tumor1
2CompletedTreatmentAdvanced Hepatocellular Carcinoma / Hepatic neoplasms malignant / Liver Cancer / Neoplasms, Hepatic1
2CompletedTreatmentAdvanced Hepatocellular Carcinoma / Inoperable Hepatocellular Carcinoma1
2CompletedTreatmentAdvanced Renal Cell Carcinoma1
2CompletedTreatmentAdvanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (Relapsed After a Cisplatin Based Treatment)1
2CompletedTreatmentAnaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Hepatosplenic T-Cell Lymphoma / Peripheral T-Cell Lymphoma (PTCL) / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma1
2CompletedTreatmentAnaplastic Large Cell Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Mantle Cell Lymphoma1
2CompletedTreatmentBladder Cancers1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentCancer of the Ovary2
2CompletedTreatmentCancer, Breast2
2CompletedTreatmentCancer, Breast / Neoplasms, Breast1
2CompletedTreatmentChildhood Hepatocellular Carcinoma / Previously Treated Childhood Rhabdomyosarcoma / Recurrent Childhood Liver Cancer / Recurrent Childhood Rhabdomyosarcoma / Recurrent Thyroid Cancer / Recurrent Wilms Tumor and Other Childhood Kidney Tumors / Thyroid Papillary Carcinoma1
2CompletedTreatmentCiliary Body and Choroid Melanoma, Medium/Large Size / Extraocular Extension Melanoma / Iris Melanoma / Metastatic Intraocular Melanoma / Recurrent Intraocular Melanoma1
2CompletedTreatmentClear Cell Renal Cell Carcinoma / Renal Cell Cancer, Recurrent / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer1
2CompletedTreatmentClear Cell Renal Cell Carcinoma / Renal Cell Carcinoma Recurrent / Stage IV Renal Cell Cancer1
2CompletedTreatmentClinically Significant Portal Hypertension1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentEffects of Chemotherapy / Malignant Neoplasm of Stomach1
2CompletedTreatmentEpithelial Mesothelioma / Recurrent Malignant Mesothelioma / Sarcomatous Mesothelioma / Stage IA Malignant Mesothelioma / Stage IB Malignant Mesothelioma / Stage II Malignant Mesothelioma / Stage III Malignant Mesothelioma / Stage IV Malignant Mesothelioma1
2CompletedTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach1
2CompletedTreatmentExtensive Stage Small Cell Lung Cancer / Refractory Small cell lung cancer1
2CompletedTreatmentExtrahepatic Bile Duct Adenocarcinoma / Gallbladder Adenocarcinoma / Gallbladder Adenocarcinoma With Squamous Metaplasia / Hilar Cholangiocarcinoma / Recurrent Extrahepatic Bile Duct Carcinoma / Recurrent Gallbladder Carcinoma / Undifferentiated Gallbladder Carcinoma / Unresectable Extrahepatic Bile Duct Carcinoma / Unresectable Gallbladder Carcinoma1
2CompletedTreatmentExtrahepatic Bile Duct Cancer / Gallbladder Cancer1
2CompletedTreatmentFallopian Tube Cancer / Neoplasms, Ovarian / Primary Peritoneal Cancer1
2CompletedTreatmentGastrinoma / Glucagonoma / Insulinoma / Metastatic Gastrointestinal Carcinoid Tumor / Neuroendocrine Tumors / Pancreatic Polypeptide Tumor / Recurrent Gastrointestinal Carcinoid Tumor / Recurrent Islet Cell Carcinoma / Somatostatinoma / WDHA Syndrome1
2CompletedTreatmentGastrointestinal Stromal Tumors1
2CompletedTreatmentGlioblastoma Multiforme (GBM)1
2CompletedTreatmentHepatocellular,Carcinoma14
2CompletedTreatmentKidney Diseases / Renal Cancers / Renal Cell Adenocarcinoma1
2CompletedTreatmentLeiomyosarcomas / Malignant Peripheral Nerve Sheath Tumour (MPNST) / Sarcomas / Synovial Sarcoma1
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)2
2CompletedTreatmentLiver Cancer2
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)5
2CompletedTreatmentLung Cancers4
2CompletedTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentMalignancies / Melanoma1
2CompletedTreatmentMalignancies / Non-Small Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentMalignant Melanoma2
2CompletedTreatmentMalignant Neoplasm of Pancreas2
2CompletedTreatmentMelanoma2
2CompletedTreatmentMelanoma Stage III or IV / No Prior Chemotherapy1
2CompletedTreatmentMetastasis / Neoplasms1
2CompletedTreatmentMetastatic Anaplastic Thyroid Cancer / Metastatic Differentiated Thyroid Cancer / Metastatic Medullary Thyroid Cancer / Metastatic Poorly Differentiated Thyroid Cancer1
2CompletedTreatmentMetastatic Bladder Cancer / Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter / Recurrent Bladder Cancer / Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter / Regional Transitional Cell Cancer of the Renal Pelvis and Ureter / Stage III Bladder Cancer / Transitional Cell Carcinoma of the Bladder1
2CompletedTreatmentMetastatic Bone Sarcomas / Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Adult Soft Tissue Sarcoma / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Osteosarcoma / Stage I Adult Soft Tissue Sarcoma / Stage II Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma1
2CompletedTreatmentMetastatic Bone Sarcomas / Relapsed Osteosarcoma1
2CompletedTreatmentMetastatic Breast Cancer (MBC)1
2CompletedTreatmentMetastatic Cancers / Renal Cancers1
2CompletedTreatmentMetastatic Colorectal Cancers2
2CompletedTreatmentMetastatic Disease / Renal Cell Adenocarcinoma2
2CompletedTreatmentMetastatic Renal Cell Carcinoma1
2CompletedTreatmentMetastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma / Recurrent Metastatic Squamous Neck Cancer With Occult Primary / Recurrent Salivary Gland Cancer / Recurrent Squamous Cell Carcinoma of the Hypopharynx / Recurrent Squamous Cell Carcinoma of the Larynx / Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity / Recurrent Squamous Cell Carcinoma of the Nasopharynx / Recurrent Squamous Cell Carcinoma of the Oropharynx / Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Recurrent Verrucous Carcinoma of the Larynx / Recurrent Verrucous Carcinoma of the Oral Cavity / Salivary Gland Squamous Cell Carcinoma / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Nasopharynx / Stage IVA Salivary Gland Cancer / Stage IVA Squamous Cell Carcinoma of the Larynx / Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVA Squamous Cell Carcinoma of the Oropharynx / Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVA Verrucous Carcinoma of the Larynx / Stage IVA Verrucous Carcinoma of the Oral Cavity / Stage IVB Salivary Gland Cancer / Stage IVB Squamous Cell Carcinoma of the Larynx / Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVB Squamous Cell Carcinoma of the Oropharynx / Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVB Verrucous Carcinoma of the Larynx / Stage IVB Verrucous Carcinoma of the Oral Cavity / Stage IVC Salivary Gland Cancer / Stage IVC Squamous Cell Carcinoma of the Larynx / Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVC Squamous Cell Carcinoma of the Oropharynx / Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVC Verrucous Carcinoma of the Larynx / Stage IVC Verrucous Carcinoma of the Oral Cavity / Tongue Cancer / Untreated Metastatic Squamous Neck Cancer With Occult Primary2
2CompletedTreatmentNeoplasms, Head and Neck1
2CompletedTreatmentNeoplasms, Ovarian1
2CompletedTreatmentNon-Small Cell Lung Cancer Recurrent / Stage IIIb Non-small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer1
2CompletedTreatmentPrimary Peritoneal Carcinoma / Recurrent Ovarian Carcinoma1
2CompletedTreatmentProstate Cancer3
2CompletedTreatmentRecurrent Fallopian Tube Carcinoma / Recurrent Ovarian Carcinoma / Recurrent Primary Peritoneal Carcinoma1
2CompletedTreatmentRecurrent Glioblastoma Multiforme1
2CompletedTreatmentRecurrent Melanoma / Stage IV Melanoma1
2CompletedTreatmentRecurrent Melanoma / Stage IV Skin Melanoma / Stages III Skin Melanoma1
2CompletedTreatmentRecurrent Ovarian Epithelial Cancer / Recurrent Primary Peritoneal Cavity Cancer1
2CompletedTreatmentRecurrent Uterine Sarcoma / Stage III Uterine Sarcoma / Stage IV Uterine Sarcoma / Uterine Carcinosarcoma1
2CompletedTreatmentRefractory Multiple Myeloma1
2CompletedTreatmentRenal Cancers1
2CompletedTreatmentRenal Cell Adenocarcinoma7
2CompletedTreatmentSarcoma, Osteogenic1
2CompletedTreatmentSarcomas1
2CompletedTreatmentSoft Tissue Sarcoma (STS)1
2CompletedTreatmentStage III Melanoma / Stage IV Melanoma1
2CompletedTreatmentStage IV Pancreatic Cancer1
2CompletedTreatmentThyroid Cancers2
2CompletedTreatmentThyroid Carcinoma1
2CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
2CompletedTreatmentChronic Chronic myelogenous leukemia1
2Not Yet RecruitingTreatmentHepatocellular,Carcinoma1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome / Chronic Myelomonocytic Leukemia / Myelodysplastic Syndrome / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Refractory Adult Acute Lymphoblastic Leukemia1
2RecruitingTreatmentBrain and Nervous System / Glioblastomas / Gliomas / Malignant Gliomas / Recurrent Adult Brain Neoplasm / WHO Grade III Glioma1
2RecruitingTreatmentCancer, Advanced / Hepatocellular,Carcinoma1
2RecruitingTreatmentCancer, Breast / Metastatic Breast Cancer (MBC) / Recurrent Breast Cancer1
2RecruitingTreatmentCholangiocarcinoma of the Extrahepatic Bile Duct / Gallbladder Cancer1
2RecruitingTreatmentDifferentiated Thyroid Cancer (DTC) / Follicular Thyroid Cancer / Poorly Differentiated Thyroid Gland Carcinoma / Thyroid Cancer, Medullary / Thyroid Cancers / Thyroid Papillary Carcinoma1
2RecruitingTreatmentFLT3-ITD Mutation / Leukemia Acute Myeloid Leukemia (AML)1
2RecruitingTreatmentHepatocellular Cancer1
2RecruitingTreatmentHepatocellular,Carcinoma5
2RecruitingTreatmentHepatocellular,Carcinoma / Portal Vein Thrombosis1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
2RecruitingTreatmentMalignant Solid Neoplasms1
2RecruitingTreatmentMetastatic Colorectal Cancer Patients With KRAS Mutated Tumors1
2RecruitingTreatmentMetastatic Renal Cell Carcinoma2
2RecruitingTreatmentNeuroblastomas1
2RecruitingTreatmentPediatric Solid Tumors1
2RecruitingTreatmentRefractory Hurthle Cell Thyroid Cancer1
2RecruitingTreatmentRefractory Pediatric AML / Refractory Pediatric Solid Tumors / Relapsed Pediatric AML / Relapsed Pediatric Solid Tumors1
2RecruitingTreatmentRhabdomyosarcomas1
2RecruitingTreatmentStage III Hepatocellular Carcinoma AJCC v8 / Stage IIIA Hepatocellular Carcinoma AJCC v8 / Stage IIIB Hepatocellular Carcinoma AJCC v7 / Stage IIIC Hepatocellular Carcinoma AJCC v7 / Stage IV Hepatocellular Carcinoma AJCC v8 / Stage IVA Hepatocellular Carcinoma AJCC v8 / Stage IVB Hepatocellular Carcinoma AJCC v81
2RecruitingTreatmentThyroid Cancer, Anaplastic1
2RecruitingTreatmentThyroid Cancers1
2TerminatedTreatmentAdenocarcinoma of the Bladder / Distal Urethral Cancer / Metastatic Bladder Cancer / Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter / Proximal Urethral Cancer / Recurrent Bladder Cancer / Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter / Recurrent Urethral Cancer / Regional Transitional Cell Cancer of the Renal Pelvis and Ureter / Squamous Cell Carcinoma of the Bladder / Stage III Bladder Cancer / Transitional Cell Carcinoma of the Bladder / Urethral Cancer Associated With Invasive Bladder Cancer1
2TerminatedTreatmentAdvanced Hepatocellular Carcinoma1
2TerminatedTreatmentAnaplastic Thyroid Cancers / Insular Thyroid Cancer / Recurrent Thyroid Cancer / Stage III Follicular Thyroid Cancer / Stage III Papillary Thyroid Cancer / Stage IV Follicular Thyroid Cancer / Stage IV Papillary Thyroid Cancer1
2TerminatedTreatmentAnaplastic Thyroid Cancers / Recurrent Thyroid Cancer1
2TerminatedTreatmentBladder Cancers1
2TerminatedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
2TerminatedTreatmentCancer, Breast5
2TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL)1
2TerminatedTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Stage I Chronic Lymphocytic Leukemia / Stage II Chronic Lymphocytic Leukemia / Stage III Chronic Lymphocytic Leukemia / Stage IV Chronic Lymphocytic Leukemia1
2TerminatedTreatmentClear Cell Renal Cell Carcinoma / Papillary Renal Cell Carcinoma / Renal Cell Cancer, Recurrent / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer1
2TerminatedTreatmentClear Cell Renal Cell Carcinoma / Renal Cell Cancer, Recurrent / Stage IV Renal Cell Cancer1
2TerminatedTreatmentHepatocellular,Carcinoma5
2TerminatedTreatmentHepatopulmonary Syndrome1
2TerminatedTreatmentKeloid Scars1
2TerminatedTreatmentLeukemia, Myelomonocytic, Chronic / Myelodysplastic Syndromes1
2TerminatedTreatmentLiver Cancer1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Non Squamous Cell Lung Cancer1
2TerminatedTreatmentLung Cancer Small Cell Lung Cancer (SCLC)1
2TerminatedTreatmentLung Cancers2
2TerminatedTreatmentMalignant Neoplasm of Stomach1
2TerminatedTreatmentMetastatic Breast Cancer (MBC)1
2TerminatedTreatmentMetastatic Hormone Refractory Prostate Cancer1
2TerminatedTreatmentMetastatic Renal Cell Carcinoma3
2TerminatedTreatmentNeoplasms, Colorectal1
2TerminatedTreatmentNeurofibromatosis1 (NF1) / Recurrent or Progressive Low-grade Glioma / Recurrent or Progressive Optic Pathway Gliomas (OPG)1
2TerminatedTreatmentRenal Cancers1
2TerminatedTreatmentRenal Cell Adenocarcinoma4
2TerminatedTreatmentSarcomas1
2Unknown StatusDiagnosticSalivary Gland Cancers1
2Unknown StatusTreatmentAdrenocortical Carcinoma1
2Unknown StatusTreatmentBladder Cancers1
2Unknown StatusTreatmentCancer, Breast1
2Unknown StatusTreatmentHepatocellular,Carcinoma5
2Unknown StatusTreatmentLiver Cancer2
2Unknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Unknown StatusTreatmentLung Cancers1
2Unknown StatusTreatmentMelanoma (Skin)2
2Unknown StatusTreatmentMesothelioma1
2Unknown StatusTreatmentNeoplasms, Colorectal1
2Unknown StatusTreatmentProstate Cancer1
2Unknown StatusTreatmentRenal Cell Adenocarcinoma2
2Unknown StatusTreatmentSarcomas1
2Unknown StatusTreatmentTesticular Cancer1
2WithdrawnTreatmentGlioblastomas / Gliosarcoma1
2WithdrawnTreatmentHepatocellular Carcinoma (HCC)1
2WithdrawnTreatmentHepatocellular,Carcinoma1
2WithdrawnTreatmentLocally Metastatic Malignant Neoplasm1
2WithdrawnTreatmentLung Cancers1
2WithdrawnTreatmentMedullary Thyroid Cancer (MTC)1
2WithdrawnTreatmentMelanoma / Recurrent Melanoma / Stage III Melanoma / Stage IV Melanoma1
2WithdrawnTreatmentProstate Cancer1
2, 3Active Not RecruitingTreatmentHCC1
2, 3CompletedTreatmentHepatocellular,Carcinoma1
2, 3CompletedTreatmentLiver Cancer1
2, 3RecruitingTreatmentChildhood Hepatocellular Carcinoma / Childhood Malignant Liver Neoplasm / Elevated Alpha-Fetoprotein / Hepatoblastomas / SMARCB1 Gene Mutation1
2, 3RecruitingTreatmentHematopoietic Stem Cell Transplantation (HSCT) / Leukemia Acute Myeloid Leukemia (AML)1
2, 3RecruitingTreatmentHepatocellular,Carcinoma2
2, 3Unknown StatusTreatmentQuality of Life1
3Active Not RecruitingTreatmentAdult Hepatocellular Carcinoma / Advanced Adult Hepatocellular Carcinoma / BCLC Stage C Adult Hepatocellular Carcinoma / BCLC Stage D Adult Hepatocellular Carcinoma / Localized Non-Resectable Adult Liver Carcinoma / Non-Resectable Hepatocellular Carcinoma / Recurrent Adult Liver Carcinoma / Recurrent Hepatocellular Carcinoma / Stage III Hepatocellular Carcinoma AJCC v7 / Stage IIIA Hepatocellular Carcinoma AJCC v7 / Stage IIIB Hepatocellular Carcinoma AJCC v7 / Stage IIIC Hepatocellular Carcinoma AJCC v7 / Stage IV Hepatocellular Carcinoma AJCC v7 / Stage IVA Hepatocellular Carcinoma AJCC v7 / Stage IVB Hepatocellular Carcinoma AJCC v7 / Unresectable Hepatocellular Carcinoma1
3Active Not RecruitingTreatmentDesmoid-Type Fibromatosis1
3Active Not RecruitingTreatmentGranulocytic Sarcoma / Leukaemia cutis / Leukemia Acute Myeloid Leukemia (AML) / Myeloid Neoplasm / Untreated Adult Acute Myeloid Leukemia / Untreated Childhood Myeloid Neoplasm1
3Active Not RecruitingTreatmentHepatocellular Carcinoma (HCC)1
3Active Not RecruitingTreatmentHepatocellular,Carcinoma3
3Active Not RecruitingTreatmentHepatocellular,Carcinoma / I.V Advanced Cancer1
3Active Not RecruitingTreatmentHepatocellular,Carcinoma / Non-Resectable Hepatocellular Carcinoma / Unresectable Hepatocellular Carcinoma1
3Active Not RecruitingTreatmentNeoplasms1
3Active Not RecruitingTreatmentNeoplasms, Kidney1
3Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
3CompletedTreatmentAdvanced Renal Cell Carcinoma2
3CompletedTreatmentCancer, Breast1
3CompletedTreatmentCarcinoma NOS / Non-Small-Cell Lung1
3CompletedTreatmentChild-Pugh A Hepatocellular Carcinoma1
3CompletedTreatmentClear Cell Renal Cell Carcinoma / Stage I Renal Cell Cancer / Stage II Renal Cell Cancer / Stage III Renal Cell Cancer1
3CompletedTreatmentHCC1
3CompletedTreatmentHepato Cellular Carcinoma (HCC)1
3CompletedTreatmentHepatocellular,Carcinoma6
3CompletedTreatmentLiver Cancer1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3CompletedTreatmentMelanoma1
3CompletedTreatmentMetastatic Renal Cell Carcinoma2
3CompletedTreatmentMucosal Melanoma / Recurrent Melanoma / Stage IIIA Skin Melanoma / Stage IIIB Skin Melanoma / Stage IIIC Skin Melanoma / Stage IV Skin Melanoma1
3CompletedTreatmentNeoplasms, Kidney1
3CompletedTreatmentNeoplasms, Thyroid1
3CompletedTreatmentRenal Cancers1
3CompletedTreatmentRenal Cell Adenocarcinoma8
3Not Yet RecruitingTreatmentHepatocellular,Carcinoma1
3RecruitingTreatmentAdult Primary Hepatocellular Carcinoma / Advanced Adult Primary Liver Cancer / Recurrent Adult Primary Liver Cancer1
3RecruitingTreatmentAdvanced Hepatocellular Carcinoma1
3RecruitingTreatmentHepatoblastomas / Hepatocellular,Carcinoma1
3RecruitingTreatmentHepatocellular Carcinoma (HCC)2
3RecruitingTreatmentHepatocellular,Carcinoma4
3RecruitingTreatmentHepatocellular,Carcinoma / Recurrences1
3TerminatedTreatmentAdenocarcinomas / Carcinoma NOS / Digestive System Diseases / Digestive System Neoplasms / Hepatocellular Carcinoma Non-resectable / Hepatocellular,Carcinoma / Liver Diseases / Neoplasms / Neoplasms by Histologic Type / Neoplasms by Site / Neoplasms, Glandular and Epithelial / Neoplasms, Hepatic / Recurrent Hepatocellular Carcinoma1
3TerminatedTreatmentAdvanced Adult Hepatocellular Carcinoma1
3TerminatedTreatmentHepatocellular,Carcinoma1
3TerminatedTreatmentHepatocellular,Carcinoma / Liver Cell Carcinoma1
3TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3TerminatedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
3Unknown StatusTreatmentAdvanced Hepatocellular Carcinoma / Carcinoma NOS / Hepatocellular,Carcinoma / Neoplasms / Neoplasms, Hepatic1
3Unknown StatusTreatmentLiver Cancer1
3Unknown StatusTreatmentMalignant Neoplasm of Pancreas1
3WithdrawnTreatmentHepatic neoplasms malignant1
4CompletedTreatmentHepatectomy / Hepatocellular,Carcinoma / Sorafenib1
4CompletedTreatmentHepatocellular,Carcinoma2
4RecruitingBasic ScienceHepatocellular,Carcinoma1
4RecruitingPreventionPortal Vein Tumor Thrombus1
4RecruitingTreatmentHepatocellular,Carcinoma1
4RecruitingTreatmentHepatocellular,Carcinoma / Metastasis1
4Unknown StatusTreatmentHepatocellular Cancer1
4WithdrawnNot AvailableRenal Cell Adenocarcinoma1
Not AvailableActive Not RecruitingNot AvailableNeoplasms, Thyroid1
Not AvailableActive Not RecruitingDiagnosticAdvanced Solid Tumors / Malignancies1
Not AvailableActive Not RecruitingTreatmentAcute myeloid leukaemia (in remission) / Acute Myeloid Leukemia With FLT3/ITD Mutation / Adult Acute Myeloid Leukemia in Remission1
Not AvailableActive Not RecruitingTreatmentAdvanced Adult Hepatocellular Carcinoma / Localized Non-Resectable Adult Hepatocellular Carcinoma / Stage III Childhood Hepatocellular Carcinoma / Stage IIIA Hepatocellular Carcinoma / Stage IIIB Hepatocellular Carcinoma / Stage IIIC Hepatocellular Carcinoma / Stage IV Childhood Hepatocellular Carcinoma / Stage IVA Hepatocellular Carcinoma / Stage IVB Hepatocellular Carcinoma1
Not AvailableActive Not RecruitingTreatmentRecurrent Childhood Brain Tumor1
Not AvailableActive Not RecruitingTreatmentRefractory Solid Tumors1
Not AvailableCompletedNot AvailableCarcinoma, Renal Cell (Advanced) / Renal Cell Adenocarcinoma2
Not AvailableCompletedNot AvailableChildhood Acute Myeloid Leukemia/Other Myeloid Malignancies1
Not AvailableCompletedNot AvailableHepatocellular,Carcinoma8
Not AvailableCompletedNot AvailableHepatocellular,Carcinoma / Renal Cell Adenocarcinoma1
Not AvailableCompletedNot AvailableRenal Cell Adenocarcinoma9
Not AvailableCompletedBasic ScienceClear Cell Renal Cell Carcinoma1
Not AvailableCompletedTreatmentCancer, Breast1
Not AvailableCompletedTreatmentRefractory Solid Tumors1
Not AvailableNot Yet RecruitingNot AvailableHepatocellular,Carcinoma1
Not AvailableNot Yet RecruitingTreatmentHCC1
Not AvailableRecruitingNot AvailableHepatocellular,Carcinoma / Neuroendocrine Tumors1
Not AvailableRecruitingNot AvailableThyroid Carcinoma1
Not AvailableRecruitingTreatmentHepatocellular,Carcinoma5
Not AvailableTerminatedNot AvailableColorectal Cancers / Hepatocellular Cancer / Lung Cancer Non-Small Cell Cancer (NSCLC) / Renal Cell Adenocarcinoma1
Not AvailableTerminatedTreatmentEsophageal Cancers1
Not AvailableTerminatedTreatmentHepatocellular,Carcinoma / Liver Cancer1
Not AvailableTerminatedTreatmentHereditary Clear Cell Renal Cell Carcinoma / Renal Cancers1
Not AvailableTerminatedTreatmentLeptomeningeal Metastases1
Not AvailableUnknown StatusNot AvailableLiver Cancer / Renal Cancers1

Pharmacoeconomics

Manufacturers
  • Bayer healthcare pharmaceuticals inc
Packagers
  • Bayer Healthcare
Dosage forms
FormRouteStrength
TabletOral200 mg
Tablet, film coatedOral200 mg
Tablet, film coatedOral200 mg/1
Prices
Unit descriptionCostUnit
Nexavar 200 mg tablet66.61USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2315715No2010-06-222018-12-22Canada
CA2359510No2007-02-132020-01-12Canada
US8618141No2003-02-112023-02-11Us
US8877933No2007-12-242027-12-24Us
US8124630No2000-01-122020-01-12Us
US8841330No2000-01-122020-01-12Us
US7235576No2000-01-122020-01-12Us
US7897623No2000-01-122020-01-12Us
US7351834No2000-01-122020-01-12Us
US9737488No2008-09-102028-09-10Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolubleFDA label
logP3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00171 mg/mLALOGPS
logP4.12ALOGPS
logP4.34ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)11.55ChemAxon
pKa (Strongest Basic)2.03ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area92.35 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity114.52 m3·mol-1ChemAxon
Polarizability41.11 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9649
Blood Brain Barrier+0.851
Caco-2 permeable-0.5138
P-glycoprotein substrateNon-substrate0.5086
P-glycoprotein inhibitor INon-inhibitor0.7141
P-glycoprotein inhibitor IINon-inhibitor0.9359
Renal organic cation transporterNon-inhibitor0.8938
CYP450 2C9 substrateNon-substrate0.6569
CYP450 2D6 substrateNon-substrate0.8212
CYP450 3A4 substrateNon-substrate0.5341
CYP450 1A2 substrateInhibitor0.6168
CYP450 2C9 inhibitorNon-inhibitor0.6171
CYP450 2D6 inhibitorNon-inhibitor0.9145
CYP450 2C19 inhibitorInhibitor0.637
CYP450 3A4 inhibitorNon-inhibitor0.7339
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6629
Ames testNon AMES toxic0.8143
CarcinogenicityNon-carcinogens0.8684
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7885 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9488
hERG inhibition (predictor II)Non-inhibitor0.6415
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Diarylethers
Alternative Parents
Trifluoromethylbenzenes / N-phenylureas / Pyridinecarboxamides / 2-heteroaryl carboxamides / Phenoxy compounds / Phenol ethers / Chlorobenzenes / Aryl chlorides / Heteroaromatic compounds / Secondary carboxylic acid amides
show 10 more
Substituents
Diaryl ether / N-phenylurea / Trifluoromethylbenzene / Pyridinecarboxamide / Pyridine carboxylic acid or derivatives / Phenoxy compound / 2-heteroaryl carboxamide / Phenol ether / Halobenzene / Chlorobenzene
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, ureas, monochlorobenzenes, (trifluoromethyl)benzenes, pyridinecarboxamide (CHEBI:50924)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. Phosphorylates MAP2K1, a...
Gene Name
BRAF
Uniprot ID
P15056
Uniprot Name
Serine/threonine-protein kinase B-raf
Molecular Weight
84436.135 Da
References
  1. Flaherty KT: Chemotherapy and targeted therapy combinations in advanced melanoma. Clin Cancer Res. 2006 Apr 1;12(7 Pt 2):2366s-2370s. [PubMed:16609060]
  2. Haluska FG, Ibrahim N: Therapeutic targets in melanoma: map kinase pathway. Curr Oncol Rep. 2006 Sep;8(5):400-5. [PubMed:16901402]
  3. Kim S, Yazici YD, Calzada G, Wang ZY, Younes MN, Jasser SA, El-Naggar AK, Myers JN: Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice. Mol Cancer Ther. 2007 Jun;6(6):1785-92. [PubMed:17575107]
  4. Eisen T, Ahmad T, Flaherty KT, Gore M, Kaye S, Marais R, Gibbens I, Hackett S, James M, Schuchter LM, Nathanson KL, Xia C, Simantov R, Schwartz B, Poulin-Costello M, O'Dwyer PJ, Ratain MJ: Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis. Br J Cancer. 2006 Sep 4;95(5):581-6. Epub 2006 Aug 1. [PubMed:16880785]
  5. Lu X, Tang X, Guo W, Ren T, Zhao H: Sorafenib induces growth inhibition and apoptosis of human chondrosarcoma cells by blocking the RAF/ERK/MEK pathway. J Surg Oncol. 2010 Dec 1;102(7):821-6. doi: 10.1002/jso.21661. [PubMed:20812347]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determin...
Gene Name
RAF1
Uniprot ID
P04049
Uniprot Name
RAF proto-oncogene serine/threonine-protein kinase
Molecular Weight
73051.025 Da
References
  1. Adnane L, Trail PA, Taylor I, Wilhelm SM: Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006;407:597-612. [PubMed:16757355]
  2. Gollob JA, Wilhelm S, Carter C, Kelley SL: Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. Semin Oncol. 2006 Aug;33(4):392-406. [PubMed:16890795]
  3. Huether A, Hopfner M, Baradari V, Schuppan D, Scherubl H: Sorafenib alone or as combination therapy for growth control of cholangiocarcinoma. Biochem Pharmacol. 2007 May 1;73(9):1308-17. Epub 2007 Jan 5. [PubMed:17266941]
  4. Cascone T, Gridelli C, Ciardiello F: Combined targeted therapies in non-small cell lung cancer: a winner strategy? Curr Opin Oncol. 2007 Mar;19(2):98-102. [PubMed:17272980]
  5. Gridelli C, Maione P, Del Gaizo F, Colantuoni G, Guerriero C, Ferrara C, Nicolella D, Comunale D, De Vita A, Rossi A: Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer. Oncologist. 2007 Feb;12(2):191-200. [PubMed:17296815]
  6. Lu X, Tang X, Guo W, Ren T, Zhao H: Sorafenib induces growth inhibition and apoptosis of human chondrosarcoma cells by blocking the RAF/ERK/MEK pathway. J Surg Oncol. 2010 Dec 1;102(7):821-6. doi: 10.1002/jso.21661. [PubMed:20812347]
  7. Smalley KS, Xiao M, Villanueva J, Nguyen TK, Flaherty KT, Letrero R, Van Belle P, Elder DE, Wang Y, Nathanson KL, Herlyn M: CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations. Oncogene. 2009 Jan 8;28(1):85-94. doi: 10.1038/onc.2008.362. Epub 2008 Sep 15. [PubMed:18794803]
  8. Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM, Lynch M: Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther. 2008 Oct;7(10):3129-40. doi: 10.1158/1535-7163.MCT-08-0013. [PubMed:18852116]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
Molecular Weight
152755.94 Da
References
  1. Lathia C, Lettieri J, Cihon F, Gallentine M, Radtke M, Sundaresan P: Lack of effect of ketoconazole-mediated CYP3A inhibition on sorafenib clinical pharmacokinetics. Cancer Chemother Pharmacol. 2006 May;57(5):685-92. Epub 2005 Aug 25. [PubMed:16133532]
  2. Adnane L, Trail PA, Taylor I, Wilhelm SM: Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006;407:597-612. [PubMed:16757355]
  3. Gridelli C, Maione P, Del Gaizo F, Colantuoni G, Guerriero C, Ferrara C, Nicolella D, Comunale D, De Vita A, Rossi A: Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer. Oncologist. 2007 Feb;12(2):191-200. [PubMed:17296815]
  4. Strumberg D: Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment. Drugs Today (Barc). 2005 Dec;41(12):773-84. [PubMed:16474853]
  5. Reddy GK, Bukowski RM: Sorafenib: recent update on activity as a single agent and in combination with interferon-alpha2 in patients with advanced-stage renal cell carcinoma. Clin Genitourin Cancer. 2006 Mar;4(4):246-8. [PubMed:16729906]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Schoffski P, Dumez H, Clement P, Hoeben A, Prenen H, Wolter P, Joniau S, Roskams T, Van Poppel H: Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review. Ann Oncol. 2006 Aug;17(8):1185-96. Epub 2006 Jan 17. [PubMed:16418310]
  2. Veronese ML, Mosenkis A, Flaherty KT, Gallagher M, Stevenson JP, Townsend RR, O'Dwyer PJ: Mechanisms of hypertension associated with BAY 43-9006. J Clin Oncol. 2006 Mar 20;24(9):1363-9. Epub 2006 Jan 30. [PubMed:16446323]
  3. Rini BI: Sorafenib. Expert Opin Pharmacother. 2006 Mar;7(4):453-61. [PubMed:16503817]
  4. Adnane L, Trail PA, Taylor I, Wilhelm SM: Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006;407:597-612. [PubMed:16757355]
  5. Lacouture ME, Desai A, Soltani K, Petronic-Rosic V, Laumann AE, Ratain MJ, Stadler WM: Inflammation of actinic keratoses subsequent to therapy with sorafenib, a multitargeted tyrosine-kinase inhibitor. Clin Exp Dermatol. 2006 Nov;31(6):783-5. Epub 2006 Jul 4. [PubMed:16824050]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
Gene Name
FLT3
Uniprot ID
P36888
Uniprot Name
Receptor-type tyrosine-protein kinase FLT3
Molecular Weight
112902.51 Da
References
  1. Auclair D, Miller D, Yatsula V, Pickett W, Carter C, Chang Y, Zhang X, Wilkie D, Burd A, Shi H, Rocks S, Gedrich R, Abriola L, Vasavada H, Lynch M, Dumas J, Trail PA, Wilhelm SM: Antitumor activity of sorafenib in FLT3-driven leukemic cells. Leukemia. 2007 Mar;21(3):439-45. Epub 2007 Jan 4. [PubMed:17205056]
  2. Lierman E, Lahortiga I, Van Miegroet H, Mentens N, Marynen P, Cools J: The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors. Haematologica. 2007 Jan;92(1):27-34. [PubMed:17229632]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Vascular endothelial growth factor binding
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
Molecular Weight
123966.895 Da
References
  1. Gollob JA: Sorafenib: scientific rationales for single-agent and combination therapy in clear-cell renal cell carcinoma. Clin Genitourin Cancer. 2005 Dec;4(3):167-74. [PubMed:16425993]
  2. Guida T, Anaganti S, Provitera L, Gedrich R, Sullivan E, Wilhelm SM, Santoro M, Carlomagno F: Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res. 2007 Jun 1;13(11):3363-9. [PubMed:17545544]
  3. Unnithan J, Rini BI: The role of targeted therapy in metastatic renal cell carcinoma. ScientificWorldJournal. 2007 Mar 2;7:800-7. [PubMed:17619763]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
Molecular Weight
109863.655 Da
References
  1. Guida T, Anaganti S, Provitera L, Gedrich R, Sullivan E, Wilhelm SM, Santoro M, Carlomagno F: Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res. 2007 Jun 1;13(11):3363-9. [PubMed:17545544]
  2. Koch CA, Gimm O, Vortmeyer AO, Al-Ali HK, Lamesch P, Ott R, Kluge R, Bierbach U, Tannapfel A: Does the expression of c-kit (CD117) in neuroendocrine tumors represent a target for therapy? Ann N Y Acad Sci. 2006 Aug;1073:517-26. [PubMed:17102120]
  3. Lierman E, Lahortiga I, Van Miegroet H, Mentens N, Marynen P, Cools J: The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors. Haematologica. 2007 Jan;92(1):27-34. [PubMed:17229632]
  4. Cascone T, Gridelli C, Ciardiello F: Combined targeted therapies in non-small cell lung cancer: a winner strategy? Curr Opin Oncol. 2007 Mar;19(2):98-102. [PubMed:17272980]
  5. Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D, Wilhelm S, Lynch M, Carter C: Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006 Dec 15;66(24):11851-8. [PubMed:17178882]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation ...
Gene Name
FGFR1
Uniprot ID
P11362
Uniprot Name
Fibroblast growth factor receptor 1
Molecular Weight
91866.935 Da
References
  1. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA: BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004 Oct 1;64(19):7099-109. [PubMed:15466206]
  2. Carlomagno F, Anaganti S, Guida T, Salvatore G, Troncone G, Wilhelm SM, Santoro M: BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst. 2006 Mar 1;98(5):326-34. [PubMed:16507829]
  3. Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S: Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006 Oct;5(10):835-44. [PubMed:17016424]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da
References
  1. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA: BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004 Oct 1;64(19):7099-109. [PubMed:15466206]
  2. Carlomagno F, Anaganti S, Guida T, Salvatore G, Troncone G, Wilhelm SM, Santoro M: BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst. 2006 Mar 1;98(5):326-34. [PubMed:16507829]
  3. Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S: Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006 Oct;5(10):835-44. [PubMed:17016424]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA: BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 2004 Oct 1;64(19):7099-109. [PubMed:15466206]
  2. Carlomagno F, Anaganti S, Guida T, Salvatore G, Troncone G, Wilhelm SM, Santoro M: BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst. 2006 Mar 1;98(5):326-34. [PubMed:16507829]
  3. Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S: Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006 Oct;5(10):835-44. [PubMed:17016424]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Gong L, Giacomini MM, Giacomini C, Maitland ML, Altman RB, Klein TE: PharmGKB summary: sorafenib pathways. Pharmacogenet Genomics. 2017 Jun;27(6):240-246. doi: 10.1097/FPC.0000000000000279. [PubMed:28362716]
  2. Holstein A, Kovacs P, Beil W: Severe hypoglycemia due to possible interaction between glibenclamide and sorafenib in a patient with hepatocellular carcinoma. Curr Drug Saf. 2013 Apr;8(2):148-52. [PubMed:23845193]
  3. Sorafenib FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Gomo C, Coriat R, Faivre L, Mir O, Ropert S, Billemont B, Dauphin A, Tod M, Goldwasser F, Blanchet B: Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4. doi: 10.1007/s10637-010-9514-3. Epub 2010 Aug 13. [PubMed:20706860]
  2. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976]
  3. Flaherty KT, Lathia C, Frye RF, Schuchter L, Redlinger M, Rosen M, O'Dwyer PJ: Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8. doi: 10.1007/s00280-011-1585-0. Epub 2011 Feb 25. [PubMed:21350850]
  4. Sugiyama M, Fujita K, Murayama N, Akiyama Y, Yamazaki H, Sasaki Y: Sorafenib and sunitinib, two anticancer drugs, inhibit CYP3A4-mediated and activate CY3A5-mediated midazolam 1'-hydroxylation. Drug Metab Dispos. 2011 May;39(5):757-62. doi: 10.1124/dmd.110.037853. Epub 2011 Jan 25. [PubMed:21266595]
  5. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Flaherty KT, Lathia C, Frye RF, Schuchter L, Redlinger M, Rosen M, O'Dwyer PJ: Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8. doi: 10.1007/s00280-011-1585-0. Epub 2011 Feb 25. [PubMed:21350850]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Flaherty KT, Lathia C, Frye RF, Schuchter L, Redlinger M, Rosen M, O'Dwyer PJ: Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8. doi: 10.1007/s00280-011-1585-0. Epub 2011 Feb 25. [PubMed:21350850]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Flaherty KT, Lathia C, Frye RF, Schuchter L, Redlinger M, Rosen M, O'Dwyer PJ: Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8. doi: 10.1007/s00280-011-1585-0. Epub 2011 Feb 25. [PubMed:21350850]
  2. Zimmerman EI, Roberts JL, Li L, Finkelstein D, Gibson A, Chaudhry AS, Schuetz EG, Rubnitz JE, Inaba H, Baker SD: Ontogeny and sorafenib metabolism. Clin Cancer Res. 2012 Oct 15;18(20):5788-95. doi: 10.1158/1078-0432.CCR-12-1967. Epub 2012 Aug 27. [PubMed:22927483]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Flaherty KT, Lathia C, Frye RF, Schuchter L, Redlinger M, Rosen M, O'Dwyer PJ: Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8. doi: 10.1007/s00280-011-1585-0. Epub 2011 Feb 25. [PubMed:21350850]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Flaherty KT, Lathia C, Frye RF, Schuchter L, Redlinger M, Rosen M, O'Dwyer PJ: Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8. doi: 10.1007/s00280-011-1585-0. Epub 2011 Feb 25. [PubMed:21350850]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Gomo C, Coriat R, Faivre L, Mir O, Ropert S, Billemont B, Dauphin A, Tod M, Goldwasser F, Blanchet B: Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4. doi: 10.1007/s10637-010-9514-3. Epub 2010 Aug 13. [PubMed:20706860]
  2. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976]
  3. Keating GM, Santoro A: Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs. 2009;69(2):223-40. doi: 10.2165/00003495-200969020-00006. [PubMed:19228077]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
The literature seems to reflect that Sorafenib is either strictly a substrate or an inhibitor.
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380]
  2. Lagas JS, van Waterschoot RA, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH: Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation. Mol Cancer Ther. 2010 Feb;9(2):319-26. doi: 10.1158/1535-7163.MCT-09-0663. Epub 2010 Jan 26. [PubMed:20103600]
  3. Wei Y, Ma Y, Zhao Q, Ren Z, Li Y, Hou T, Peng H: New use for an old drug: inhibiting ABCG2 with sorafenib. Mol Cancer Ther. 2012 Aug;11(8):1693-702. doi: 10.1158/1535-7163.MCT-12-0215. Epub 2012 May 16. [PubMed:22593228]
  4. Huang WC, Hsieh YL, Hung CM, Chien PH, Chien YF, Chen LC, Tu CY, Chen CH, Hsu SC, Lin YM, Chen YJ: BCRP/ABCG2 inhibition sensitizes hepatocellular carcinoma cells to sorafenib. PLoS One. 2013 Dec 31;8(12):e83627. doi: 10.1371/journal.pone.0083627. eCollection 2013. [PubMed:24391798]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380]
  2. Lagas JS, van Waterschoot RA, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH: Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation. Mol Cancer Ther. 2010 Feb;9(2):319-26. doi: 10.1158/1535-7163.MCT-09-0663. Epub 2010 Jan 26. [PubMed:20103600]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Transmembrane transporter activity
Specific Function
Can activate specifically hydrolysis of GTP bound to RAC1 and CDC42, but not RALA. Mediates ATP-dependent transport of S-(2,4-dinitrophenyl)-glutathione (DNP-SG) and doxorubicin (DOX) and is the ma...
Gene Name
RALBP1
Uniprot ID
Q15311
Uniprot Name
RalA-binding protein 1
Molecular Weight
76062.86 Da
References
  1. Singhal SS, Sehrawat A, Sahu M, Singhal P, Vatsyayan R, Rao Lelsani PC, Yadav S, Awasthi S: Rlip76 transports sunitinib and sorafenib and mediates drug resistance in kidney cancer. Int J Cancer. 2010 Mar 15;126(6):1327-38. doi: 10.1002/ijc.24767. [PubMed:19626587]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Hu S, Mathijssen RH, de Bruijn P, Baker SD, Sparreboom A: Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro-in vivo correlations. Br J Cancer. 2014 Feb 18;110(4):894-8. doi: 10.1038/bjc.2013.811. Epub 2014 Jan 7. [PubMed:24398510]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:41