SORAFENIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H16ClF3N4O3
Molecular Weight	464.825
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1

InChI

InChIKey=MLDQJTXFUGDVEO-UHFFFAOYSA-N

InChI=1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)

HIDE SMILES / InChI

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
BAY 43-9006: early clinical data in patients with advanced solid malignancies.	2002	12369852
Drug-drug interaction pharmacokinetic study with the Raf kinase inhibitor (RKI) BAY 43-9006 administered in combination with irinotecan (CPT-11) in patients with solid tumors.	2003 Dec	14692719
Antitumor effect and potentiation or reduction in cytotoxic drug activity in human colon carcinoma cells by the Raf kinase inhibitor (RKI) BAY 43-9006.	2003 Dec	14692718
Gateways to clinical trials.	2004 Apr	15148527
B-RAF is a therapeutic target in melanoma.	2004 Aug 19	15208680
Use of mitogenic cascade blockers for treatment of C-Raf induced lung adenoma in vivo: CI-1040 strongly reduces growth and improves lung structure.	2004 Jun 1	15171791
How thyroid tumors start and why it matters: kinase mutants as targets for solid cancer pharmacotherapy.	2004 Nov	15531713
Novel agents for the treatment of advanced kidney cancer.	2004 Oct	16163253
Validation of a liquid chromatography assay for the quantification of the Raf kinase inhibitor BAY 43-9006 in small volumes of mouse serum.	2004 Sep 25	15282098
Improving outcomes in advanced malignant melanoma: update on systemic therapy.	2005	15819587
Clinical trials referral resource. Current clinical trials of BAY 43-9006, Part 1.	2005 Apr	15934518
Raf kinase as a target for anticancer therapeutics.	2005 Apr	15827342
Subungual splinter hemorrhages: a clinical window to inhibition of vascular endothelial growth factor receptors?	2005 Aug 16	16103482
Raf kinase inhibitors in oncology.	2005 Feb	15665559
The Raf kinase inhibitor BAY 43-9006 reduces cellular uptake of platinum compounds and cytotoxicity in human colorectal carcinoma cell lines.	2005 Feb	15655409
Multi-kinase inhibitors create buzz at ASCO.	2005 Jun	15940222
Novel kinase inhibitors in renal cell carcinoma: progressive development of static agents.	2005 Mar	15717945
Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors.	2005 Mar 15	15781657
Angiogenesis and lung cancer: prognostic and therapeutic implications.	2005 May 10	15886312
Update on angiogenesis inhibitors.	2005 Nov	16224236
Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors.	2005 Oct	16006586
The role of Mcl-1 downregulation in the proapoptotic activity of the multikinase inhibitor BAY 43-9006.	2005 Oct 20	16007148
Results of a phase I trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer.	2005 Sep	16197622
Spinal cord metastasis of a non-neurofibromatosis type-1 malignant peripheral nerve sheath tumor: an unusual manifestation of a rare tumor.	2005 Sep	16193390
Raf: a strategic target for therapeutic development against cancer.	2005 Sep 20	16170185
Drug approval triggers debate on future direction for cancer treatments.	2006 Feb	16521324
Raf-1 kinase associates with Hepatitis C virus NS5A and regulates viral replication.	2006 Jan 23	16405965
Targeting Raf-kinase: molecular rationales and translational issues.	2006 Jun	16760274
VEGF-targeted therapy in renal cell carcinoma: active drugs and active choices.	2006 Mar	16507216
Isolation and characterization of dominant and recessive IL-3-independent hematopoietic transformants.	2006 Oct 26	16702946

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 21:24:38 GMT 2025` Edited by `admin` on `Mon Mar 31 21:24:38 GMT 2025`
Record UNII	9ZOQ3TZI87
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SORAFENIB

Official Name

English

BAY 43-9006

Preferred Name

English

SORAFENIB [USAN]

Common Name

English

SORAFENIB [MART.]

Common Name

English

SORAFENIB [EMA EPAR]

Common Name

English

2-PYRIDINECARBOXAMIDE, 4-(4-((((4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)AMINO)CARBONYL)AMINO)PHENOXY)-N-METHYL-

Systematic Name

English

SORAFENIB [MI]

Common Name

English

4-(4-(3-(4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)UREIDO)PHENOXY)-N(SUP 2)-METHYLPYRIDINE-2-CARBOXAMIDE

Systematic Name

English

Sorafenib [WHO-DD]

Common Name

English

SORAFENIB [VANDF]

Common Name

English

BAY-43-9006

Code

English

sorafenib [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825