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Details

Stereochemistry ACHIRAL
Molecular Formula C21H16ClF3N4O3
Molecular Weight 464.825
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SORAFENIB

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

Description

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

Approval Year

Target InfoCondition Info
PMID

PMID

TitleDatePMID
Regulation of c-Raf-1: therapeutic implications.
2003 Aug
Novel agents for the treatment of advanced kidney cancer.
2004 Oct
Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment.
2005 Dec
Sorafenib: scientific rationales for single-agent and combination therapy in clear-cell renal cell carcinoma.
2005 Dec
Gateways to clinical trials.
2005 Nov
Update on angiogenesis inhibitors.
2005 Nov
Targeted therapy in renal cell carcinoma.
2005 Oct
Synergistic inhibition of human melanoma proliferation by combination treatment with B-Raf inhibitor BAY43-9006 and mTOR inhibitor Rapamycin.
2005 Oct 28
Results of a phase I trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer.
2005 Sep
Spinal cord metastasis of a non-neurofibromatosis type-1 malignant peripheral nerve sheath tumor: an unusual manifestation of a rare tumor.
2005 Sep
Targeting multiple signal transduction pathways in lung cancer.
2005 Sep
Targeting angiogenesis with vascular endothelial growth factor receptor small-molecule inhibitors: novel agents with potential in lung cancer.
2005 Sep
Raf: a strategic target for therapeutic development against cancer.
2005 Sep 20
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
The role of adjuvant therapy in non-metastatic RCC.
2006 Apr
What's new in pancreatic cancer treatment pipeline?
2006 Apr
Molecular targets in melanoma from angiogenesis to apoptosis.
2006 Apr 1
Chemotherapy and targeted therapy combinations in advanced melanoma.
2006 Apr 1
Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review.
2006 Aug
Sorafenib is a potent inhibitor of FIP1L1-PDGFRalpha and the imatinib-resistant FIP1L1-PDGFRalpha T674I mutant.
2006 Aug 15
Drug approval triggers debate on future direction for cancer treatments.
2006 Feb
[Progress in therapeutic strategy for renal cell carcinoma].
2006 Feb
The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells.
2006 Feb 1
[Therapy strategies for advanced renal cell carcinoma].
2006 Jan
Second- and third-line treatments in non-small cell lung cancer.
2006 Jan
Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer.
2006 Jan 1
Raf-1 kinase associates with Hepatitis C virus NS5A and regulates viral replication.
2006 Jan 23
Targeting Raf-kinase: molecular rationales and translational issues.
2006 Jun
Comparative integromics on VEGF family members.
2006 Jun
Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma.
2006 Jun 1
Sorafenib: recent update on activity as a single agent and in combination with interferon-alpha2 in patients with advanced-stage renal cell carcinoma.
2006 Mar
Emerging antiangiogenic agents in lung cancer.
2006 Mar
Molecule of the month. Sorafenib.
2006 Mar
Multi-target inhibitors in non-small cell lung cancer (NSCLC).
2006 Mar
VEGF-targeted therapy in renal cell carcinoma: active drugs and active choices.
2006 Mar
Sorafenib.
2006 Mar
Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome?
2006 Mar
BRAF is a therapeutic target in aggressive thyroid carcinoma.
2006 Mar 1
BAY 43-9006 inhibition of oncogenic RET mutants.
2006 Mar 1
Targeted therapy for metastatic renal cell carcinoma.
2006 Mar 13
Mechanisms of hypertension associated with BAY 43-9006.
2006 Mar 20
Treatment for advanced kidney cancer.
2006 Mar-Apr
New drugs: abatacept, sorafenib, and nelarabine.
2006 Mar-Apr
Targeted therapy for cytokine-refractory metastatic renal cell carcinoma, and treatment in the community.
2006 May
Emerging efficacy endpoints for targeted therapies in advanced renal cell carcinoma.
2006 May
Results of a Phase I trial of sorafenib (BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors.
2006 May
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 May
The place of VEGF inhibition in the current management of renal cell carcinoma.
2006 May 8
Isolation and characterization of dominant and recessive IL-3-independent hematopoietic transformants.
2006 Oct 26
Sorafenib is efficacious and tolerated in combination with cytotoxic or cytostatic agents in preclinical models of human non-small cell lung carcinoma.
2007 Feb
Patent

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
Name Type Language
SORAFENIB
EMA EPAR   INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
SORAFENIB [USAN]
Common Name English
SORAFENIB [MART.]
Common Name English
SORAFENIB [EMA EPAR]
Common Name English
SORAFENIB [WHO-DD]
Common Name English
2-PYRIDINECARBOXAMIDE, 4-(4-((((4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL)AMINO)CARBONYL)AMINO)PHENOXY)-N-METHYL-
Systematic Name English
BAY 43-9006
Code 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 [VANDF]
Common Name English
BAY-43-9006
Code English
SORAFENIB [INN]
Common Name English
Classification Tree Code System Code
WHO-VATC QL01XE05
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
WHO-ATC L01XE05
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
NDF-RT N0000175076
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
EMA ASSESSMENT REPORTS NEXAVAR (AUTHORIZED: CARCINOMA, HEPATOCELLULAR, CARINOMA, RENAL CELL)
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
LIVERTOX 894
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
NDF-RT N0000175605
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
Code System Code Type Description
LactMed
284461-73-0
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
INN
8234
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
RXCUI
495881
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY RxNorm
NCI_THESAURUS
C61948
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
MESH
C471405
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
PUBCHEM
216239
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY SWITZERF
EPA CompTox
284461-73-0
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
WIKIPEDIA
SORAFENIB
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
ChEMBL
CHEMBL1336
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
HSDB
284461-73-0
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
IUPHAR
5711
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
DRUG BANK
DB00398
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
MERCK INDEX
M10116
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY Merck Index
CAS
284461-73-0
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY
EVMPD
SUB23139
Created by admin on Tue Mar 06 11:17:00 UTC 2018 , Edited by admin on Tue Mar 06 11:17:00 UTC 2018
PRIMARY