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Synonyms: BAY 43-9006 | BAY-439006 | Nexavar®
sorafenib is an approved drug (FDA (2005), EMA (2006))
Compound class:
Synthetic organic
Comment: Sorafenib is a broad spectrum Type-2 kinase inhibitor targeting VEGFR2, VEGFR3, PDGFRβ, Flt3, and KIT and non-receptor kinases RAF1 and BRAF [8].
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖
View more information in the IUPHAR Pharmacology Education Project: sorafenib |
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Summary of Clinical Use  |
| Sorafenib was originally approved for treatment of approved for the treatment of advanced renal cell carcinoma, and further approved for advanced hepatocellular carcinoma. In November 2013, the FDA expanded the approval of sorafenib to allow it to be used to treat late-stage (metastatic) differentiated thyroid cancer. The clinically administered form is the sorafenib tosylate salt (PubChem CID 406563). |
| Mechanism Of Action and Pharmacodynamic Effects |
| Sorafenib is a multikinase inhibitor that decreases tumour cell proliferation in vitro. Sorafenib inhibits tumour growth of a broad spectrum of human tumour xenografts in athymic mice accompanied by a reduction of tumour angiogenesis. It is believed that sorfenib inhibits genetic transcription involved in cell proliferation and angiogenesis by targeting the Raf/Mek/Erk pathway. Specifically, sorafenib inhibits the activity of targets present in the tumour cell (CRAF, BRAF, V600E BRAF (VAR_018629), c-KIT, and FLT-3) and in the tumour vasculature (CRAF, VEGFR-2, VEGFR-3, and PDGFR-β). RAF kinases are serine/threonine kinases, whereas c-KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-β are receptor tyrosine kinases. |
| Pharmacokinetics |
| Absorption/Distribution |
| Following oral administration sorafenib reaches peak plasma concentrations in approximately 3 hours with a mean relative bioavailability of 38-49% for the tablet form, when compared to an oral solution. In vitro binding of sorafenib to human plasma proteins is 99.5 %. |
| Biotransformation/Metabolism |
| Metabolism occurs primarily in the liver by CYP3A4 and UGT1A9-mediated glucuronidation. The main circulating metabolite of sorafenib in plasma is the pyridine N-oxide which shows in vitro potency similar to that of sorafenib. At steady-state this metabolite comprises approximately 9-16% of circulating analytes. |
| Elimination |
| Elimination in the feces (77%) and urine (19%- as glucuronidated metabolites). |
| Population pharmacokinetics |
| Pharmacokinetics of sorafenib are not significantly affected by age or body weight. Total exposure is 30% lower in Asians than in white patients. |
| Organ function impairment |
| Mild (Child-Pugh class A) and moderate (Child-Pugh class B) hepatic function impairment decreases exposure to sorafenib by 23% and 65%, respectively (not studied in subjects with severe hepatic function impairment). In clinical trials and clinical pharmacology studies no relationship is observed between sorafenib exposure and renal function in subjects with normal renal function, mild, moderate or severe renal impairment (no data is available in patients requiring dialysis). |
| External links |
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For extended ADME data see the following: Electronic Medicines Compendium (eMC) Drugs.com European Medicines Agency (EMA) |
