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Identification
NamePanitumumab
Accession NumberDB01269
Typebiotech
Groupsapproved, investigational
Description

Panitumumab (ABX-EGF) is a recombinant human IgG2 monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). This drug is an antineoplastic agent.

Protein structureNo structure small
Protein chemical formulaNot Available
Protein average weightNot Available
Sequences
Synonyms
SynonymLanguageCode
ABX-EGFNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
VectibixAmgen
Brand mixturesNot Available
CategoriesNot Available
CAS number339177-26-3
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor the treatment of EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens.
PharmacodynamicsPanitumumab is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human Epidermal Growth Factor Receptor (EGFR). EGFR is a transmembrane glycoprotein that belongs to the subfamily of type I receptor tyrosine kinases. Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, including those of the colon and rectum. Interaction of EGFR with its normal ligands causes phosphorylation and activation of a series of intracellular proteins that will in turn regulate the transcription of genes involved with cellular growth and survival, motility, and prolieration. Signal transduction through EGFR leads to the activation of the wild type KRAS gene, but the presence of an activating somatic mutation of the KRAS gene within a cancer cell can result in the dysregulation of signaling pathways and resistance to EGFR inhibitor therapy.
Mechanism of actionPanitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production, and internalization of the EGFR.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life7.5 days (range: 4-11 days)
Clearance
  • 4.9+/- 1.4 mL/kg/day [Following single-dose administrations of panitumumab as 1-hour infusions]
ToxicityPanitumumab was shown to cause skin, ocular and mucosal related toxicities in 90% of patients receiving panitumumab. Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, and abscesses requiring incisions and drainage, were reported.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Panitumumab Action PathwayDrug actionSMP00475
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous drip
Prices
Unit descriptionCostUnit
Vectibix 400 mg/20ml Solution 20ml Vial4349.4USDvial
Vectibix 100 mg/5ml Solution 5ml Vial1059.24USDvial
Vectibix 100 mg/5 ml vial203.7USDml
Vectibix 200 mg/10 ml vial203.7USDml
Vectibix 400 mg/20 ml vial203.7USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Foon KA, Yang XD, Weiner LM, Belldegrun AS, Figlin RA, Crawford J, Rowinsky EK, Dutcher JP, Vogelzang NJ, Gollub J, Thompson JA, Schwartz G, Bukowski RM, Roskos LK, Schwab GM: Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):984-90. Pubmed
  2. Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG: Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 2001 Apr;38(1):17-23. Pubmed
  3. Wu M, Rivkin A, Pham T: Panitumumab: human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer. Clin Ther. 2008 Jan;30(1):14-30. Pubmed
  4. Saadeh CE, Lee HS: Panitumumab: a fully human monoclonal antibody with activity in metastatic colorectal cancer. Ann Pharmacother. 2007 Apr;41(4):606-13. Epub 2007 Mar 13. Pubmed
  5. Keating GM: Panitumumab: a review of its use in metastatic colorectal cancer. Drugs. 2010 May 28;70(8):1059-78. doi: 10.2165/11205090-000000000-00000. Pubmed
External Links
ResourceLink
UniProtP01859
PharmGKBPA162373091
Drugs.comhttp://www.drugs.com/cdi/panitumumab.html
WikipediaPanitumumab
ATC CodesL01XC08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

1. Epidermal growth factor receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: suppressor

Components

Name UniProt ID Details
Epidermal growth factor receptor P00533 Details

References:

  1. Lynch DH, Yang XD: Therapeutic potential of ABX-EGF: a fully human anti-epidermal growth factor receptor monoclonal antibody for cancer treatment. Semin Oncol. 2002 Feb;29(1 Suppl 4):47-50. Pubmed
  2. Cohen RB: Epidermal growth factor receptor as a therapeutic target in colorectal cancer. Clin Colorectal Cancer. 2003 Feb;2(4):246-51. Pubmed
  3. Foon KA, Yang XD, Weiner LM, Belldegrun AS, Figlin RA, Crawford J, Rowinsky EK, Dutcher JP, Vogelzang NJ, Gollub J, Thompson JA, Schwartz G, Bukowski RM, Roskos LK, Schwab GM: Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):984-90. Pubmed
  4. Segaert S, Van Cutsem E: Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol. 2005 Sep;16(9):1425-33. Epub 2005 Jul 12. Pubmed
  5. Heymach JV, Nilsson M, Blumenschein G, Papadimitrakopoulou V, Herbst R: Epidermal growth factor receptor inhibitors in development for the treatment of non-small cell lung cancer. Clin Cancer Res. 2006 Jul 15;12(14 Pt 2):4441s-4445s. Pubmed
  6. Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG: Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 2001 Apr;38(1):17-23. Pubmed
  7. Keating GM: Spotlight on panitumumab in metastatic colorectal cancerdagger. BioDrugs. 2010 Aug 1;24(4):275-8. Pubmed
  8. Wu M, Rivkin A, Pham T: Panitumumab: human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer. Clin Ther. 2008 Jan;30(1):14-30. Pubmed
  9. Saadeh CE, Lee HS: Panitumumab: a fully human monoclonal antibody with activity in metastatic colorectal cancer. Ann Pharmacother. 2007 Apr;41(4):606-13. Epub 2007 Mar 13. Pubmed
  10. Jean GW, Shah SR: Epidermal growth factor receptor monoclonal antibodies for the treatment of metastatic colorectal cancer. Pharmacotherapy. 2008 Jun;28(6):742-54. Pubmed
  11. Keating GM: Panitumumab: a review of its use in metastatic colorectal cancer. Drugs. 2010 May 28;70(8):1059-78. Pubmed
  12. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments
Drug created on May 16, 2007 14:12 / Updated on September 03, 2011 16:56