Drug/Small Molecule:
sorafenib

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

Links to Unannotated Labels

These links are to labels associated with sorafenib that have not been annotated by PharmGKB.

  1. DailyMed - DrugLabel PA166105290

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all sorafenib variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs17868320 234578428C>T, 524687C>T, 85039C>T, 855+32405C>T, 855+51220C>T
C > T
Intronic
No VIP available CA VA
rs8175347 233760235_233760236TA[5][6][7][8], 5-TA insertion in promoter, 7-TA insertion in promoter, 8-TA insertion in promoter, UGT1A1*28, UGT1A1*36, UGT1A1*37, microsatellite, short tandem repeat
(TA)6 > (TA)8
(TA)6 > (TA)5
(TA)6 > (TA)7
Not Available
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Sorafenib tosylate
  • sorafenib
Trade Names
  • Nexavar
Brand Mixture Names

PharmGKB Accession Id:
PA7000

Description

Sorafenib (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.

Source: Drug Bank

Indication

For the treatment of patients with advanced renal cell carcinoma.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

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-beta). 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.

Source: Drug Bank

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 xenografts in athymic mice. A reduction in tumor angiogenesis occurs in some tumor xenograft models.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

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.

Source: Drug Bank

Protein Binding

99.5%

Source: Drug Bank

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.

Source: Drug Bank

Half-Life

25-48 hours

Source: Drug Bank

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.

Source: Drug Bank

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.

Source: Drug Bank

Chemical Properties

Chemical Formula

C21H16ClF3N4O3

Source: Drug Bank

Isomeric SMILES

CNC(=O)c1cc(ccn1)Oc2ccc(cc2)NC(=O)Nc3ccc(c(c3)C(F)(F)F)Cl

Source: OpenEye

Canonical SMILES

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

Source: Drug Bank

Average Molecular Weight

464.825

Source: Drug Bank

Monoisotopic Molecular Weight

464.08630272

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Sorafenib Pharmacodynamics
    Mechanism of action of sorafenib
  1. VEGF Signaling Pathway
    Model endothelial cell displaying genes of the VEGF signalling pathway and the sites at which bevacizumab, sorafenib, sunitinib, brivanib and cilengitide are known to act.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
BRAF (source: Drug Bank)
FLT3 (source: Drug Bank)
FLT4 (source: Drug Bank)
KDR (source: Drug Bank)
KIT (source: Drug Bank)
PDGFRB (source: Drug Bank)
RAF1 (source: Drug Bank)

Drug Interactions

Drug Description
sorafenib Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank)
sorafenib The strong CYP2C8 inhibitor, Sorafenib, may decrease the metabolism and clearance of oral Tretinoin. Consider alternate therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Sorafenib is initiated, discontinued to dose changed. (source: Drug Bank)

Curated Information ?

Publications related to sorafenib: 20

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Expression of SLC22A1 variants may affect the response of hepatocellular carcinoma and cholangiocarcinoma to sorafenib. Hepatology (Baltimore, Md.). 2013. Herraez Elisa, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Sorafenib hepatobiliary disposition: mechanisms of hepatic uptake and disposition of generated metabolites. Drug metabolism and disposition: the biological fate of chemicals. 2013. Swift Brandon, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Estimation of renal cell carcinoma treatment effects from disease progression modeling. Clinical pharmacology and therapeutics. 2013. Maitland M L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomics as a risk mitigation strategy for chemotherapeutic cardiotoxicity. Pharmacogenomics. 2013. Jensen Brian C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effects of vascular endothelial growth factor signaling inhibition on human erythropoiesis. The oncologist. 2013. Bhatta Sumita S, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Early Sorafenib-Induced Toxicity Is Associated with Drug Exposure and UGTIA9 Genetic Polymorphism in Patients with Solid Tumors: A Preliminary Study. PloS one. 2012. Boudou-Rouquette Pascaline, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Efficacy and safety of sorafenib in a subset of patients with advanced soft tissue sarcoma from a Phase II randomized discontinuation trial. Investigational new drugs. 2011. Pacey Simon, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Two drug interaction studies of sirolimus in combination with sorafenib or sunitinib in patients with advanced malignancies. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Gangadhar Tara C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clinical pharmacology and therapeutics. 2010. Stegmeier F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Vascular endothelial growth factor pathway. Pharmacogenetics and genomics. 2010. Maitland Michael L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A dosing/cross-development study of the multikinase inhibitor sorafenib in patients with pulmonary arterial hypertension. Clinical pharmacology and therapeutics. 2010. Gomberg-Maitland M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Sorafenib, a dual Raf kinase/vascular endothelial growth factor receptor inhibitor has significant anti-myeloma activity and synergizes with common anti-myeloma drugs. Oncogene. 2010. Ramakrishnan V, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib. Cancer chemotherapy and pharmacology. 2009. Meza-Junco Judith, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Ambulatory monitoring detects sorafenib-induced blood pressure elevations on the first day of treatment. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Maitland Michael L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs. 2009. Keating Gillian M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A phase II clinical trial of sorafenib in androgen-independent prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008. Dahut William L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Results from an in vitro and a clinical/pharmacological phase I study with the combination irinotecan and sorafenib. European journal of cancer (Oxford, England : 1990). 2007. Mross K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Sorafenib in advanced clear-cell renal-cell carcinoma. The New England journal of medicine. 2007. Escudier Bernard, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer research. 2004. Wilhelm Scott M, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
50419-488-58
DrugBank:
DB00398
PDB:
BAX
ChEBI:
50924
PubChem Compound:
216239
PubChem Substance:
46505329
789424
BindingDB:
16673
ChemSpider:
187440
HET:
BAX
Therapeutic Targets Database:
DAP000006
FDA Drug Label at DailyMed:
b50667e4-5ebc-4968-a646-d605058dbef0

Clinical Trials

These are trials that mention sorafenib and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.