DT-Web

DB00002 - Cetuximab


Identification
Name Cetuximab
Accession Number DB00002 (BIOD00071, BTD00071)
Type biotech
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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 145781.6000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For 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.
Mechanism 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.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Single 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
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Epidermal growth factor receptor
Name Epidermal growth factor receptor
Gene Name EGFR
Pharmacological action yes
Actions antagonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.6984
Low affinity immunoglobulin gamma Fc region receptor III-B
Name Low affinity immunoglobulin gamma Fc region receptor III-B
Gene Name FCGR3B
Pharmacological action unknown
Actions Not Available
References
  • 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
DTHybrid score 1.5739
Complement C1r subcomponent
Name Complement C1r subcomponent
Gene Name C1R
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1.4818
Complement C1q subcomponent subunit A
Name Complement C1q subcomponent subunit A
Gene Name C1QA
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1.4992
Complement C1q subcomponent subunit B
Name Complement C1q subcomponent subunit B
Gene Name C1QB
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1.5
Complement C1q subcomponent subunit C
Name Complement C1q subcomponent subunit C
Gene Name C1QC
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1.5
Low affinity immunoglobulin gamma Fc region receptor III-A
Name Low affinity immunoglobulin gamma Fc region receptor III-A
Gene Name FCGR3A
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
DTHybrid score 1.5735
Complement C1s subcomponent
Name Complement C1s subcomponent
Gene Name C1S
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1.1144
High affinity immunoglobulin gamma Fc receptor I
Name High affinity immunoglobulin gamma Fc receptor I
Gene Name FCGR1A
Pharmacological action unknown
Actions Not Available
References
  • 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
DTHybrid score 1.6597
Low affinity immunoglobulin gamma Fc region receptor II-a
Name Low affinity immunoglobulin gamma Fc region receptor II-a
Gene Name FCGR2A
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
DTHybrid score 1.5821
Low affinity immunoglobulin gamma Fc region receptor II-b
Name Low affinity immunoglobulin gamma Fc region receptor II-b
Gene Name FCGR2B
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1.5776
Low affinity immunoglobulin gamma Fc region receptor II-c
Name Low affinity immunoglobulin gamma Fc region receptor II-c
Gene Name FCGR2C
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1.5877

Predictions


Id Partner name Gene Name Score
75 B-lymphocyte antigen CD20 MS4A1 0.368
724 Interleukin-2 receptor alpha chain IL2RA 0.2111
717 Interleukin-2 receptor subunit beta IL2RB 0.2111
777 Tumor necrosis factor TNF 0.1699
567 Receptor tyrosine-protein kinase erbB-2 ERBB2 0.1694
744 Myeloid cell surface antigen CD33 CD33 0.1557
93 CAMPATH-1 antigen CD52 0.1474
757 Fusion glycoprotein F0 F 0.147
4875 Fusion glycoprotein F0 F 0.147
1733 Vitronectin VTN 0.1334
793 T-cell surface antigen CD2 CD2 0.1302
5901 T-cell surface glycoprotein CD3 zeta chain CD247 0.1247
1789 Lymphotoxin-alpha LTA 0.1247
302 T-cell surface glycoprotein CD3 epsilon chain CD3E 0.1247
5900 T-cell surface glycoprotein CD3 gamma chain CD3G 0.1247
5899 T-cell surface glycoprotein CD3 delta chain CD3D 0.1246
1269 Tumor necrosis factor receptor superfamily member 1B TNFRSF1B 0.1246
1783 Intercellular adhesion molecule 1 ICAM1 0.1174
647 Integrin alpha-4 ITGA4 0.1173
488 Integrin alpha-IIb ITGA2B 0.1156
2039 Integrin beta-3 ITGB3 0.1139
572 Integrin alpha-L ITGAL 0.1081
183 Vascular endothelial growth factor A VEGFA 0.1057
955 Complement C5 C5 0.1033
5898 Complement C3 C3 0.103
3811 Cytochrome P450 19A1 CYP19A1 0.0687
554 Low-density lipoprotein receptor LDLR 0.0664
290 Prostaglandin G/H synthase 2 PTGS2 0.0526
933 Proto-oncogene tyrosine-protein kinase Src SRC 0.0482
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0436
1588 Multidrug resistance protein 1 ABCB1 0.0341
5300 Antigen peptide transporter 1 TAP1 0.0229
4512 Cytochrome P450 3A4 CYP3A4 0.0225
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0224
4118 Cytochrome P450 3A5 CYP3A5 0.0218
587 Serum albumin ALB 0.0176
660 T-cell surface glycoprotein CD1a CD1A 0.0172
6063 Major histocompatibility complex class I-related gene protein MR1 0.0172
5955 T-cell surface glycoprotein CD4 CD4 0.0172
6065 Integrin beta-1 ITGB1 0.0172
6066 Integrin alpha-V ITGAV 0.0172
3950 Cell division protein kinase 9 CDK9 0.0171
3968 Cell division protein kinase 8 CDK8 0.0171
4924 Cytochrome P450 2C8 CYP2C8 0.016
5787 Angiopoietin-1 receptor TEK 0.0158
3959 Cell division protein kinase 4 CDK4 0.015
3482 Cell division protein kinase 7 CDK7 0.0148
3955 Cell division protein kinase 6 CDK6 0.0138
942 T-lymphocyte activation antigen CD86 CD86 0.0138
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.013
6016 Cytochrome P450 2C19 CYP2C19 0.0129
4119 Cytochrome P450 2D6 CYP2D6 0.0125
1742 D-HSCDK2 CDK2deltaT 0.0119
1771 Cell division control protein 2 homolog CDK1 0.0119
3321 Cell division control protein 2 homolog CRK2 0.0119
1058 Cell division protein kinase 5 CDK5 0.0116
6024 Cytochrome P450 1A1 CYP1A1 0.0115
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0113
4757 Cytochrome P450 2C9 CYP2C9 0.0087
1995 Sodium channel protein type 9 subunit alpha SCN9A 0.0085
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0082
862 Multidrug resistance-associated protein 1 ABCC1 0.0079
4200 Cytochrome P450 1A2 CYP1A2 0.0078
1152 Glycogen phosphorylase, muscle form PYGM 0.0077
2240 Cell division protein kinase 2 CDK2 0.0064
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0063
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0062
1898 Cytochrome P450 1B1 CYP1B1 0.0062
6106 Cytochrome P450 2C18 CYP2C18 0.0056
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0055
118 Organic cation/carnitine transporter 2 SLC22A5 0.0049
5718 Cytochrome P450 2A6 CYP2A6 0.0046
6030 Cytochrome P450 2B6 CYP2B6 0.0042
6107 Cytochrome P450 3A7 CYP3A7 0.0041
4878 Glycoprotein hormones alpha chain CGA 0.0024
1072 Granzyme B GZMB 0.0024
4189 Alpha-galactosidase A GLA 0.0024
1052 Cytotoxic T-lymphocyte protein 4 CTLA4 0.0024
4889 Ig epsilon chain C region IGHE 0.0024
4877 Beta-mannanase man 0.0024
4871 Endo-beta-N-acetylglucosaminidase F3 endOF3 0.0024
4850 Beta-2-glycoprotein 1 APOH 0.0024
4852 Reticulon-4 receptor RTN4R 0.0024
4880 Membrane cofactor protein CD46 0.0024
4856 CD209 antigen CD209 0.0024
4869 Major capsid protein A430L 0.0024
4845 ADAM 33 ADAM33 0.0024
1563 Platelet glycoprotein Ib alpha chain GP1BA 0.0024
1354 Beta-glucuronidase GUSB 0.0024
442 Envelope glycoprotein gp41 0.0024
4859 Envelope glycoprotein env 0.0024
4882 Dipeptidyl aminopeptidase-like protein 6 DPP6 0.0024
4721 Beta-1,4-mannanase manA 0.0024
3352 Structural polyprotein Not Available 0.0024
3628 Structural polyprotein Not Available 0.0024
4892 Structural polyprotein Not Available 0.0024
1184 Interferon beta IFNB1 0.0021
6858 Inactive carboxylesterase 4 CES1P1 0.0021
4857 Zinc-alpha-2-glycoprotein AZGP1 0.0021
4193 Atrial natriuretic peptide clearance receptor NPR3 0.0021
4890 Hemagglutinin HA 0.0021
6566 Hemagglutinin Not Available 0.0021
4861 Interleukin-6 receptor alpha chain IL6R 0.0021
119 Carcinoembryonic antigen-related cell adhesion molecule 1 CEACAM1 0.0021
1379 Interleukin-12 subunit beta IL12B 0.0021
3837 Cytokine receptor common beta chain CSF2RB 0.0021
3444 Cyanovirin-N Not Available 0.002
18 High affinity immunoglobulin epsilon receptor subunit alpha FCER1A 0.002
1859 Prostatic acid phosphatase ACPP 0.002
2998 Sialic acid-binding Ig-like lectin 7 SIGLEC7 0.002
852 Heparin cofactor 2 SERPIND1 0.002
3258 Mannosyl-oligosaccharide alpha-1,2-mannosidase MSDC 0.002
3140 Hemagglutinin-neuraminidase HN 0.002
3609 Hemagglutinin-neuraminidase HN 0.002
6120 Cation-independent mannose-6-phosphate receptor IGF2R 0.002
2297 Genome polyprotein Not Available 0.002
2322 Genome polyprotein Not Available 0.002
2694 Genome polyprotein Not Available 0.002
2719 Genome polyprotein Not Available 0.002
2860 Genome polyprotein Not Available 0.002
2928 Genome polyprotein Not Available 0.002
3160 Genome polyprotein Not Available 0.002
3260 Genome polyprotein Not Available 0.002
4783 Genome polyprotein Not Available 0.002
5726 Genome polyprotein Not Available 0.002
5779 Genome polyprotein Not Available 0.002
5867 Genome polyprotein Not Available 0.002
6253 Genome polyprotein Not Available 0.002
6301 Genome polyprotein Not Available 0.002
6380 Genome polyprotein Not Available 0.002
6381 Genome polyprotein Not Available 0.002
6437 Genome polyprotein Not Available 0.002
6520 Genome polyprotein Not Available 0.002
6521 Genome polyprotein Not Available 0.002
6652 Genome polyprotein Not Available 0.002
6734 Genome polyprotein Not Available 0.002
6735 Genome polyprotein Not Available 0.002
6736 Genome polyprotein Not Available 0.002
6737 Genome polyprotein Not Available 0.002
6738 Genome polyprotein Not Available 0.002
6739 Genome polyprotein Not Available 0.002
6744 Genome polyprotein Not Available 0.002
6748 Genome polyprotein Not Available 0.002
6894 Genome polyprotein Not Available 0.002
6898 Genome polyprotein Not Available 0.002
4666 Fucose-binding lectin PA-IIL lecB 0.0019
2372 Bifunctional tail protein 9 0.0019
4787 Envelope glycoprotein gp160 env 0.0019
4820 Envelope glycoprotein gp160 env 0.0019
5727 Envelope glycoprotein gp160 env 0.0019
2577 Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase MAN1B1 0.0018
3480 Mannan endo-1,4-beta-mannosidase manA 0.0017
64 Neuraminidase NA 0.0017
641 Neuraminidase NA 0.0017
2676 Neuraminidase NA 0.0017
3026 Neuraminidase NA 0.0017
3519 Neuraminidase NA 0.0017
6007 Neuraminidase NA 0.0017
595 Fibrinogen alpha chain FGA 0.0017
1782 Neutrophil gelatinase-associated lipocalin LCN2 0.0017
1439 Lactotransferrin LTF 0.0017
1243 Cathepsin D CTSD 0.0016
2430 Chondroitinase B cslB 0.0016
958 Insulin-like growth factor 1 receptor IGF1R 0.0016
6307 Ig gamma-2 chain C region IGHG2 0.0015
309 Antithrombin-III SERPINC1 0.0015
2581 Chondroitinase AC cslA 0.0015
6847 Lactase-phlorizin hydrolase LCT 0.0015
6500 Phospholipase A2 PLA2G1B 0.0015
2207 Rhodopsin RHO 0.0014
4785 Ig gamma-1 chain C region IGHG1 0.0013
4604 Liver carboxylesterase 1 CES1 0.0013
76 Nitric-oxide synthase, brain NOS1 0.0013
952 Dipeptidyl peptidase 4 DPP4 0.0011
3923 Cholinesterase BCHE 0.0011
20 Prostaglandin G/H synthase 1 PTGS1 0.001
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