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Identification
NameCetuximab
Accession NumberDB00002  (BIOD00071, BTD00071)
TypeBiotech
GroupsApproved
Description

Epidermal growth factor receptor binding FAB. Cetuximab is composed of the Fv (variable; antigen-binding) regions of the 225 murine EGFr monoclonal antibody specific for the N-terminal portion of human EGFr with human IgG1 heavy and kappa light chain constant (framework) regions.

Protein structureDb00002
Protein chemical formulaC6484H10042N1732O2023S36
Protein average weight145781.6000
Sequences
>Cetuximab heavy chain
QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYN
TPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYYDYEFAYWGQGTLVTVSAA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSPKSCDKTHTCPPCPAPELL
GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ
YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Cetuximab light chain
DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPS
RFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGA
Download FASTA Format
Synonyms
SynonymLanguageCode
Anti EGFRNot AvailableNot Available
IMC-C225Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ErbituxImClone Systems Inc
Brand mixturesNot Available
Categories
CAS number205923-56-4
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 treatment of EGFR-expressing metastatic colorectal cancer in patients who are refractory to other irinotecan-based chemotherapy regimens. Cetuximab is also indicated for treatment of squamous cell carcinoma of the head and neck in conjucntion with radiation therapy.
PharmacodynamicsUsed in the treatment of colorectal cancer, cetuximab binds specifically to the epidermal growth factor receptor (EGFr, HER1, c-ErbB-1) on both normal and tumor cells. EGFr is over-expressed in many colorectal cancers. Cetuximab competitively inhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforming growth factor–alpha. Binding of cetuximab to the EGFr blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased matrix metalloproteinase secretion and reduced vascular endothelial growth factor production.
Mechanism of actionCetuximab binds to the epidermal growth factor receptor (EGFr) on both normal and tumor cells. EGFr is over-expressed in many colorectal cancers. Cetuximab competitively inhibits the binding of epidermal growth factor (EGF) and TGF alpha, thereby reducing their effects on cell growth and metastatic spread.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life114 hrs
ClearanceNot Available
ToxicitySingle doses of cetuximab higher than 500 mg/m2 have not been tested. There is no experience with overdosage in human clinical trials.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Cetuximab Action PathwayDrug actionSMP00474
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Low affinity immunoglobulin gamma Fc region receptor II-a
Gene symbol: FCGR2A
UniProt: P12318
rs1801274 Not AvailableH allelleIncreased progression free survival17704420
Low affinity immunoglobulin gamma Fc region receptor III-A
Gene symbol: FCGR3A
UniProt: P08637
rs396991 Not AvailableA > CBetter response to drug therapy (longer progression free survival) with the F allele17704420
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada13404171999-03-022016-03-02
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity-0.413Not Available
isoelectric point8.48Not Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
GenbankJ00228
PharmGKBPA10040
RxListhttp://www.rxlist.com/cgi/generic3/erbitux.htm
Drugs.comhttp://www.drugs.com/cdi/cetuximab.html
WikipediaCetuximab
ATC CodesL01XC06
AHFS CodesNot Available
PDB Entries
FDA labelshow(73.8 KB)
MSDSNot Available
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Epidermal growth factor receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Epidermal growth factor receptor P00533 Details

References:

  1. Hosokawa N, Yamamoto S, Uehara Y, Hori M, Tsuchiya KS: Effect of thiazinotrienomycin B, an ansamycin antibiotic, on the function of epidermal growth factor receptor in human stomach tumor cells. J Antibiot (Tokyo). 1999 May;52(5):485-90. Pubmed
  2. Wakita H, Takigawa M: Activation of epidermal growth factor receptor promotes late terminal differentiation of cell-matrix interaction-disrupted keratinocytes. J Biol Chem. 1999 Dec 24;274(52):37285-91. Pubmed
  3. Suwa T, Ueda M, Jinno H, Ozawa S, Kitagawa Y, Ando N, Kitajima M: Epidermal growth factor receptor-dependent cytotoxic effect of anti-EGFR antibody-ribonuclease conjugate on human cancer cells. Anticancer Res. 1999 Sep-Oct;19(5B):4161-5. Pubmed
  4. Burke P, Schooler K, Wiley HS: Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking. Mol Biol Cell. 2001 Jun;12(6):1897-910. Pubmed
  5. Viloria-Petit A, Crombet T, Jothy S, Hicklin D, Bohlen P, Schlaeppi JM, Rak J, Kerbel RS: Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Res. 2001 Jul 1;61(13):5090-101. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Low affinity immunoglobulin gamma Fc region receptor III-B

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor III-B O75015 Details

References:

  1. Snyder LC, Astsaturov I, Weiner LM: Overview of monoclonal antibodies and small molecules targeting the epidermal growth factor receptor pathway in colorectal cancer. Clin Colorectal Cancer. 2005 Nov;5 Suppl 2:S71-80. Pubmed

3. Complement C1r subcomponent

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1r subcomponent P00736 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

4. Complement C1q subcomponent subunit A

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit A P02745 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

5. Complement C1q subcomponent subunit B

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit B P02746 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

6. Complement C1q subcomponent subunit C

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit C P02747 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

7. Low affinity immunoglobulin gamma Fc region receptor III-A

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor III-A P08637 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, Chang HM, Borucka E, Lurje G, Sherrod AE, Iqbal S, Groshen S, Lenz HJ: FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol. 2007 Aug 20;25(24):3712-8. Pubmed

8. Complement C1s subcomponent

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1s subcomponent P09871 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

9. High affinity immunoglobulin gamma Fc receptor I

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
High affinity immunoglobulin gamma Fc receptor I P12314 Details

References:

  1. Negri DR, Tosi E, Valota O, Ferrini S, Cambiaggi A, Sforzini S, Silvani A, Ruffini PA, Colnaghi MI, Canevari S: In vitro and in vivo stability and anti-tumour efficacy of an anti-EGFR/anti-CD3 F(ab’)2 bispecific monoclonal antibody. Br J Cancer. 1995 Oct;72(4):928-33. Pubmed

10. Low affinity immunoglobulin gamma Fc region receptor II-a

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-a P12318 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, Chang HM, Borucka E, Lurje G, Sherrod AE, Iqbal S, Groshen S, Lenz HJ: FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol. 2007 Aug 20;25(24):3712-8. Pubmed

11. Low affinity immunoglobulin gamma Fc region receptor II-b

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-b P31994 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

12. Low affinity immunoglobulin gamma Fc region receptor II-c

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-c P31995 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on July 31, 2011 23:04