Name: | sorafenib |
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PubChem Compound ID: | 11843539 |
Molecular formula: | C21H16ClF3N4O3 |
Molecular weight: | 466.817 g/mol |
Name: | sorafenib |
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Name (isomeric): | DB00398 |
Drug Type: | small molecule |
Synonyms: |
Sorafenib tosylate
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Brand: | Nexavar |
Category: | Anticancer Agents, Antineoplastic Agents, Protein Kinase Inhibitors |
CAS number: | 284461-73-0 |
Indication: | For the treatment of patients with advanced renal cell carcinoma. |
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Pharmacology: |
Sorafenib is a multikinase inhibitor targeting several serine/threonine and receptor tyrosine kinases. It is commonly available as a tosylate salt. Sorafenib is a multikinase inhibitor that decreases tumor cell proliferation in vitro. Sorafenib inhibits tumor growth of the murine renal cell carcinoma, RENCA, and several other human tumor xen...
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Mechanism of Action: |
Sorafenib 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 ki...
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Absorption: | The mean relative bioavailability is 38-49% for the tablet form, when compared to an oral solution. With a high-fat meal, bioavailability is reduced by 29% compared to administration in the fasted state. |
Protein binding: | 99.5% |
Biotransformation: | Sorafenib 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: | The 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. |
Affected organisms: | Humans and other mammals |
Drug interaction: |
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