SORAFENIB TOSYLATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H16ClF3N4O3.C7H8O3S
Molecular Weight	637.027
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=C(C=C1)S(O)(=O)=O.CNC(=O)C2=NC=CC(OC3=CC=C(NC(=O)NC4=CC=C(Cl)C(=C4)C(F)(F)F)C=C3)=C2

InChI

InChIKey=IVDHYUQIDRJSTI-UHFFFAOYSA-N

InChI=1S/C21H16ClF3N4O3.C7H8O3S/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;1-6-2-4-7(5-3-6)11(8,9)10/h2-11H,1H3,(H,26,30)(H2,28,29,31);2-5H,1H3,(H,8,9,10)

HIDE SMILES / InChI

Molecular Formula	C7H8O3S
Molecular Weight	172.202
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021923s016lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase B-raf 21 Target ID: CHEMBL5145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20812347	Inhibitor 8504
Serine/threonine-protein kinase RAF 11 Target ID: CHEMBL1906 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20812347	Inhibitor 8504
Vascular endothelial growth factor receptor 11 Target ID: CHEMBL2095227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16757355	Inhibitor 8504
Tyrosine-protein kinase receptor FLT3 42 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17229632	Inhibitor 8504
Platelet-derived growth factor receptor beta 56 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17545544	Inhibitor 8504
Stem cell growth factor receptor 57 Target ID: CHEMBL1936 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17545544	Inhibitor 8504
Tyrosine-protein kinase receptor RET 16 Target ID: CHEMBL2041 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15466206	Inhibitor 8504	50.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hepatocellular carcinoma 83 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021923s016lbl.pdf	Primary	Approved 8583	NEXAVAR Approved Use NEXAVAR 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 Date 2005
Differentiated thyroid carcinoma 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021923s016lbl.pdf https://www.ncbi.nlm.nih.gov/books/NBK6979/	Primary	Approved 8583	NEXAVAR Approved Use NEXAVAR 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 Date 2005
Renal cell carcinoma 33 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021923s016lbl.pdf	Primary	Approved 8583	NEXAVAR Approved Use NEXAVAR 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 Date 2005

C_max

Value	Dose	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	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

T_1/2

Value	Dose	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

F_unbound

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: https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/16061863/	unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/16061863/	DLT: Hypertension, Rash... Other AEs: Dyspnea, Rash... Dose limiting toxicities: Hypertension (grade 3, 33%) Rash (grade 2, 33%) Rash (grade 3, 67%) Other AEs: Dyspnea (grade 3, 33%) 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%) Sources: https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/16061863/
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: https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/16061863/	unhealthy, Mean age 53.7 years Health Status: unhealthy Age Group: Mean age 53.7 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/16061863/	Other AEs: Ascites, Constipation... Other AEs: Ascites (grade 3, 33%) 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%) Sources: https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/16061863/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021923lbl.pdf https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/27981711/	unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021923lbl.pdf https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/27981711/	Other AEs: Diarrhea... Other AEs: Diarrhea (22.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021923lbl.pdf https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/27981711/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021923lbl.pdf https://pubmed.ncbi.nlm.nih.gov/27981711/	unhealthy, Median age 57 years Health Status: unhealthy Age Group: Median age 57 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021923lbl.pdf https://pubmed.ncbi.nlm.nih.gov/27981711/	Other AEs: Hand and foot skin reaction, Desquamation... Other AEs: Hand and foot skin reaction (10%) 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%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021923lbl.pdf https://pubmed.ncbi.nlm.nih.gov/27981711/
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf	unhealthy, Median age 58 years Health Status: unhealthy Age Group: Median age 58 years Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf	Other AEs: Hypertension, Fatigue... Other AEs: Hypertension (grade 3, 2%) 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%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf
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: https://pubmed.ncbi.nlm.nih.gov/15613696/	unhealthy, Median age 60 years Health Status: unhealthy Age Group: Median age 60 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15613696/	DLT: Diarrhea... Dose limiting toxicities: Diarrhea (grade 3, 20%) Sources: https://pubmed.ncbi.nlm.nih.gov/15613696/
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: https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/15613696/	unhealthy, Median age 60 years Health Status: unhealthy Age Group: Median age 60 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/15613696/	Disc. AE: Pancreatitis... AEs leading to discontinuation/dose reduction: Pancreatitis (grade 3, 6.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/21789159/ https://pubmed.ncbi.nlm.nih.gov/15613696/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP2B6 926 CYP2C8 1057 UGT1A1 246 UGT1A9 148 CaV channel 4 P-gp 1741	UGT1A9 423 CYP2C8 810 UGT1A7 249 UGT1A1 479 UGT1A3 470 UGT1A4 399 UGT1A6 343 UGT1A8 323 UGT1A10 331 UGT2B4 278 UGT2B7 456 UGT2B15 236 UGT2B17 237 P-gp 2052	CYP1A2 832

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=6 Page: -	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=6 Page: -	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=47 Page: -	yes [IC50 0.84 uM]
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=48 Page: -	yes [Ki 1.5 uM]
UGT1A9 155	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=48 Page: -	yes [Ki 1.5 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf#page=45 Page: -	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: -
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf#page=45 Page: -	yes [Ki 2.4 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf#page=45 Page: -	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: -
CYP3A4 2633	inhibitor 4027 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: -
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf#page=45 Page: -	yes [Ki 6.2 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_MedR.pdf#page=45 Page: -	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: -
CaV channel 5	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_PharmR.pdf#page=32 Page: -	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=5 Page: -	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: -
UGT1A1 479	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	no
UGT1A10 331	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	no
UGT1A3 470	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	no
UGT1A4 399	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	no
UGT1A6 343	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	no
UGT1A8 323	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	no
UGT2B15 236	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	no
UGT2B17 237	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	no
UGT2B4 278	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	no
UGT2B7 456	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	no
UGT1A9 423	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=5 Page: -	yes [Km 5.8 uM]
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	yes
UGT1A7 249	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=28 Page: -	yes
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_BioPharmR.pdf#page=47 Page: -	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
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021923_s000_Nexavar_PharmR.pdf#page=32 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:50924	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50924
ChemicalBook	CB42545752	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB42545752
eMolecules	902486	https://www.emolecules.com/cgi-bin/more?vid=902486
MolPort	MolPort-003-850-270	https://www.molport.com/shop/molecule-link/MolPort-003-850-270
ZINC	ZINC000001493878	http://zinc15.docking.org/substances/ZINC000001493878

PubMed

Title	Date	PubMed
Sorafenib is efficacious and tolerated in combination with cytotoxic or cytostatic agents in preclinical models of human non-small cell lung carcinoma.	2007-02	16724239
Isolation and characterization of dominant and recessive IL-3-independent hematopoietic transformants.	2006-10-26	16702946
Sorafenib is a potent inhibitor of FIP1L1-PDGFRalpha and the imatinib-resistant FIP1L1-PDGFRalpha T674I mutant.	2006-08-15	16645167
Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review.	2006-08	16418310
Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma.	2006-06-01	16636341
Targeting Raf-kinase: molecular rationales and translational issues.	2006-06	16760274
Comparative integromics on VEGF family members.	2006-06	16685460
The place of VEGF inhibition in the current management of renal cell carcinoma.	2006-05-08	16508632
Treatment for advanced kidney cancer.	2006-05-05	16673450
Targeted therapy for cytokine-refractory metastatic renal cell carcinoma, and treatment in the community.	2006-05	16773842
Emerging efficacy endpoints for targeted therapies in advanced renal cell carcinoma.	2006-05	16773841
Results of a Phase I trial of sorafenib (BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors.	2006-05	16500908
Pharmacodynamic monitoring of BAY 43-9006 (Sorafenib) in phase I clinical trials involving solid tumor and AML/MDS patients, using flow cytometry to monitor activation of the ERK pathway in peripheral blood cells.	2006-05	16498671
New drugs: abatacept, sorafenib, and nelarabine.	2006-04-11	16602235
Molecular targets in melanoma from angiogenesis to apoptosis.	2006-04-01	16609062
Chemotherapy and targeted therapy combinations in advanced melanoma.	2006-04-01	16609060
The role of adjuvant therapy in non-metastatic RCC.	2006-04	16672131
What's new in pancreatic cancer treatment pipeline?	2006-04	16549330
Mechanisms of hypertension associated with BAY 43-9006.	2006-03-20	16446323
Targeted therapy for metastatic renal cell carcinoma.	2006-03-13	16465192
BRAF is a therapeutic target in aggressive thyroid carcinoma.	2006-03-01	16533790
BAY 43-9006 inhibition of oncogenic RET mutants.	2006-03-01	16507829
Sorafenib: recent update on activity as a single agent and in combination with interferon-alpha2 in patients with advanced-stage renal cell carcinoma.	2006-03	16729906
Emerging antiangiogenic agents in lung cancer.	2006-03	16640800
Molecule of the month. Sorafenib.	2006-03	16628266
Multi-target inhibitors in non-small cell lung cancer (NSCLC).	2006-03	16608985
VEGF-targeted therapy in renal cell carcinoma: active drugs and active choices.	2006-03	16507216
Sorafenib.	2006-03	16503817
Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome?	2006-03	16426838
The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells.	2006-02-01	16452220
Drug approval triggers debate on future direction for cancer treatments.	2006-02	16521324
[Progress in therapeutic strategy for renal cell carcinoma].	2006-02	16484851
Raf-1 kinase associates with Hepatitis C virus NS5A and regulates viral replication.	2006-01-23	16405965
Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer.	2006-01-01	16397036
[Therapy strategies for advanced renal cell carcinoma].	2006-01	16372186
Second- and third-line treatments in non-small cell lung cancer.	2006-01	16343367
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.	2006	16757355
Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment.	2005-12	16474853
Sorafenib: scientific rationales for single-agent and combination therapy in clear-cell renal cell carcinoma.	2005-12	16425993
Gateways to clinical trials.	2005-11	16357953
Update on angiogenesis inhibitors.	2005-11	16224236
Synergistic inhibition of human melanoma proliferation by combination treatment with B-Raf inhibitor BAY43-9006 and mTOR inhibitor Rapamycin.	2005-10-28	16255777
Targeted therapy in renal cell carcinoma.	2005-10	16185167
Raf: a strategic target for therapeutic development against cancer.	2005-09-20	16170185
Results of a phase I trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer.	2005-09	16197622
Spinal cord metastasis of a non-neurofibromatosis type-1 malignant peripheral nerve sheath tumor: an unusual manifestation of a rare tumor.	2005-09	16193390
Targeting multiple signal transduction pathways in lung cancer.	2005-09	16159418
Targeting angiogenesis with vascular endothelial growth factor receptor small-molecule inhibitors: novel agents with potential in lung cancer.	2005-09	16159417
Novel agents for the treatment of advanced kidney cancer.	2004-10	16163253
Regulation of c-Raf-1: therapeutic implications.	2003-08	16258435

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Mon Mar 31 18:09:52 GMT 2025` Edited by `admin` on `Mon Mar 31 18:09:52 GMT 2025`
Record UNII	5T62Q3B36J
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

SORAFENIB TOSILATE

Preferred Name

English

SORAFENIB TOSYLATE

Official Name

English

SORAFENIB TOSYLATE [ORANGE BOOK]

Common Name

English

4-(4-(((4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)CARBAMOYL)AMINO)PHENOXY)-N-METHYLPYRIDINE-2-CARBOXAMIDE 4-METHYLBENZENESULPHONATE

Systematic Name

English

4-(4-(((4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)CARBAMOYL)AMINO)PHENOXY)-N-METHYLPYRIDINE-2-CARBOXAMIDE 4-METHYLBENZENESULFONATE

Systematic Name

English

SORAFENIB TOSYLATE [USP-RS]

Common Name

English

4-(4-(3-(4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)UREIDO)PHENOXY)-N2-METHYLPYRIDINE-2-CARBOXAMIDE MONO (4-METHYLBENZENESULFONATE)

Systematic Name

English

SORAFENIB TOSYLATE [USAN]

Common Name

English

SORAFENIB TOSYLATE [MI]

Common Name

English

SORAFENIB TOSILATE [JAN]

Common Name

English

SORAFENIB TOSYLATE [USP MONOGRAPH]

Common Name

English

NEXAVAR

Brand Name

English

BAY 54-9085

Code

English

1-[4-Chloro-3-(trifluoromethyl)phenyl]-3-[4-[[2-(methylcarbamoyl)pyridin-4-yl]oxy]phenyl]urea mono(4-methylbenzenesulfonate)

Systematic Name

English

SORAFENIB TOSILATE [EP MONOGRAPH]

Common Name

English

Sorafenib tosilate [WHO-DD]

Common Name

English

SORAFENIB TOSILATE [MART.]

Common Name

English

BAY-54-9085

Code

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/06/364