Product Name

Cetuximab

CAS Number

205923-56-4

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Product Name:
Cetuximab
CAS Number:
205923-56-4
Indication:
Cetuximab, used in combination with irinotecan, is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy. Cetuximab administered as a single agent is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are intolerant to irinotecan-based chemotherapy.
Mode of Action:

Cetuximab 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.

Pharmacodynamics:

Used 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.

Toxicity:

Pulmonary Toxicity Interstitial lung disease (ILD) was reported in 3 of 633 (<0.5%) patients with advanced colorectal cancer receiving cetuximab. Interstitial pneumonitis with non-cardiogenic pulmonary edema resulting in death was reported in one case. Two patients had pre-existing fibrotic lung disease and experienced an acute exacerbation of their disease while receiving cetuximab in combination with irinotecan. In the clinical investigational program, an additional case of interstitial pneumonitis was reported in a patient with head and neck cancer treated with cetuximab and cisplatin. The onset of symptoms occurred between the fourth and eleventh doses of treatment in all reported cases.

ATC:
L01XC06
PubChem:
BTD00071
DrugBank:
DB00002 (BTD00071, BIOD00071)
Formula:
C6484H10042N1732O2023
Molecular Mass:
145781.6
Synonyms:
Cetuximab, Cétuximab, Cetuximab, Cetuximabum, Immunoglobulin G 1 (human-mouse monoclonal C 225 gamma 1 – chain anti-human epidermal growt factor receptor), disulfide wit human-mouse monoclonal C 225 kappa – chain, dimer
General Reference:
General Reference:
  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:10480573 ]
  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:10601294 ]
  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:10628369 ]
  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:11408594 ]
  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:11431346 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Schrag D: The price tag on progress–chemotherapy for colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):317-9. [PubMed:15269308 ]
  8. 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:16336752 ]

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