Sorafenib (CHEM002531)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (19)XML
Record Information
Version1.0
Creation Date2009-07-30 17:59:09 UTC
Update Date2026-05-14 16:37:33 UTC
Accession NumberCHEM002531
Identification
Common NameSorafenib
ClassSmall Molecule
DescriptionSorafenib (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.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
Contaminant Type
  • Amide
  • Amine
  • Anticancer Agent
  • Antineoplastic Agent
  • Drug
  • Ester
  • Ether
  • Human Neurotoxin
  • Metabolite
  • Organic Compound
  • Organochloride
  • Organofluoride
  • PMT
  • Protein Kinase Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
4-(4-((((4-Chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-2-pyridinecarboxamideChEBI
N-(4-Chloro-3-(trifluoromethyl)phenyl)-n'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)ureaChEBI
SorafenibumChEBI
Sorafenib tosylateHMDB
4-(4-(3-(4-Chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxyllic acid methyamide-4-methylbenzenesulfonateHMDB
NexavarHMDB
Sorafenib N-oxideHMDB
Sorafenib N oxideHMDB
4-(4-(3-(4-Chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxylic acid methyamide-4-methylbenzenesulfonateHMDB
Chemical FormulaC21H16ClF3N4O3
Average Molecular Mass464.825 g/mol
Monoisotopic Mass464.086 g/mol
CAS Registry Number284461-73-0
IUPAC Name4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide
Traditional Namesorafenib
SMILESCNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1
InChI IdentifierInChI=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)
InChI KeyMLDQJTXFUGDVEO-UHFFFAOYSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassEthers
Direct ParentDiarylethers
Alternative Parents
Substituents
  • Diaryl ether
  • Trifluoromethylbenzene
  • N-phenylurea
  • Pyridine carboxylic acid or derivatives
  • Pyridinecarboxamide
  • 2-heteroaryl carboxamide
  • Phenoxy compound
  • Phenol ether
  • Halobenzene
  • Chlorobenzene
  • Benzenoid
  • Pyridine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Urea
  • Secondary carboxylic acid amide
  • Carbonic acid derivative
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityInsoluble
Predicted Properties
PropertyValueSource
Water Solubility0.0017 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity114.52 m³·mol⁻¹ChemAxon
Polarizability41.11 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-022j-2972400000-d028d5e696594206a526Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0130900000-b23ba9e8bd12e0916813Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00rg-0490300000-db91bca5efaa6389647bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4r-3950000000-ae1180c0143c97f5e1f8Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-01ox-0550900000-6151f8a0f4158ca5b6afSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0890300000-869fd311854027fc3daeSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-3910000000-ad78334ecc783ea7c79aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0000900000-b1201d450369389781afSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01b9-0050900000-638480ee259c1d75f5a2Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00dr-0592200000-cc7aee9246b29d89cb4eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0900000000-d85fcc5d4d516b9d75fdSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0900000000-59cfe242fba11ec110aaSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-1900000000-ffd2c146e4b4655d855dSpectrum
Toxicity Profile
Route of ExposureThe 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.
Mechanism of ToxicitySorafenib 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.
MetabolismSorafenib 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
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesSorafenib is indicated for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma.
Minimum Risk LevelNot Available
Health EffectsHand-foot skin reaction and rash represent the most common adverse reactions; may increase the risk of bleeding (1)
SymptomsThe 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.
TreatmentThere is no specific treatment for NEXAVAR (Sorafenib ) overdose. (1)
Concentrations
Not Available
DrugBank IDDB00398
HMDB IDHMDB0014542
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkSorafenib
Chemspider ID187440
ChEBI ID50924
PubChem Compound ID216239
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot 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.

MSDSNot Available
General References
1. FDA label