Cetuximab
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Identification
- Summary
Cetuximab is an endothelial growth factor receptor binding fragment used to treat colorectal cancer as well as squamous cell carcinoma of the head and neck.
- Brand Names
- Erbitux
- Generic Name
- Cetuximab
- DrugBank Accession Number
- DB00002
- Background
Cetuximab is a recombinant chimeric human/mouse IgG1 monoclonal antibody that competitively binds to epidermal growth factor receptor (EGFR) and competitively inhibits the binding of epidermal growth factor (EGF).4 EGFR is a member of the ErbB family of receptor tyrosine kinases found in both normal and tumour cells; it is responsible for regulating epithelial tissue development and homeostasis.9 EGFR has been implicated in various types of cancer, as it is often overexpressed in malignant cells 4 and EGFR overexpression has been linked to more advanced disease and poor prognosis.3 EGFR is often mutated in certain types of cancer and serves as a driver of tumorigenesis.9 In vitro, cetuximab was shown to mediate anti-tumour effects in numerous cancer cell lines and human tumour xenografts.3
Approved by the FDA in February 2004 under the brand name ERBITUX, cetuximab is used for the treatment of head and neck cancer and metastatic, KRAS wild-type colorectal cancer, and metastatic colorectal cancer with a BRAF V600E mutation.3,13 It has also been investigated in advanced colorectal cancer, EGFR-expressing non-small cell lung cancer (NSCLC), and unresectable squamous cell skin cancer.12 Cetuximab is administered via intravenous infusion and is used as monotherapy or in combination with other chemotherapies, including platinum agents, radiation therapy, leucovorin, fluorouracil, and irinotecan.11
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6484H10042N1732O2023S36
- Protein Average Weight
- 145781.6 Da
- Sequences
>Cetuximab heavy chain QVQLKQSGPGLVQPSQSLSITCTVSGFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYN TPFTSRLSINKDNSKSQVFFKMNSLQSNDTAIYYCARALTYYDYEFAYWGQGTLVTVSAA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Cetuximab light chain DILLTQSPVILSVSPGERVSFSCRASQSIGTNIHWYQQRTNGSPRLLIKYASESISGIPS RFSGSGSGTDFTLSINSVESEDIADYYCQQNNNWPTTFGAGTKLELKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- Therapeutic Targets Database: TTD Biologic drug sequences in fasta format [Link]
- Synonyms
- Cetuximab
- Cétuximab
- Cetuximabum
- External IDs
- ABP-494
- BMS 564717
- C-225
- C225
- CMAB-009
- CMAB009
- IMC-225
- IMC-C225
- MOAB C225
Pharmacology
- Indication
Cetuximab indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy. It is indicated for treating a recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with fluorouracil. It is indicated for recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.11
Cetuximab is also indicated for K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test in combination with FOLFIRI, a chemotherapy combination that includes leucovorin, fluorouracil, and irinotecan; in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy; or as monotherapy in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan.11
Additionally, cetuximab is also indicated for metastatic colorectal cancer that is BRAF V600E mutation-positive (as determined by an FDA-approved test) in combination with encorafenib but only after prior therapy.13
Cetuximab is not indicated for the treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown.11
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Locally advanced squamous cell carcinomas of the head and neck (scchn) •••••••••••• ••••••••• ••••••• ••••••••• Used in combination to treat Metastatic colorectal cancer Regimen in combination with: Irinotecan (DB00762) •••••••••••• ••••••••• •••••••••• •• •• •••••••••••• ••••• •••••••••• •• •••••••••••••••• •••••••••••• ••••••••• Used in combination to treat Metastatic colorectal cancer Regimen in combination with: Leucovorin (DB00650), Irinotecan (DB00762), Fluorouracil (DB00544) •••••••••••• ••••••••• •••••••••• •• •• •••••••••••• •••• ••••••••• Treatment of Metastatic colorectal cancer •••••••••••• ••••••••••• •• ••••••••••• ••••••••• •••••••••• •• •• •••••••••••• •••• ••••••••• Treatment of Metastatic colorectal cancer •••••••••••• •••••••••• •••••••• •• •••••••••••• ••• •••••••••••••••• ••••••••••••• ••••••••• •••••••••• •• •• •••••••••••• •••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Cetuximab is an anticancer agent that works by inhibiting the growth and survival of epidermal growth factor receptor (EGFR)-expressing tumour cells with high specificity and higher affinity than epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), which are natural ligands of EGFR.12 Cetuximab works by inhibiting the growth and survival of EGFR-positive tumours.3 In vitro, it promotes antibody-dependent cellular cytotoxicity (ADCC) against certain human tumour types. On the contrary, cetuximab does not exert its anti-tumour effects on human tumour xenografts lacking EGFR expression.3,11
Cetuximab potentiates the cytotoxic effects of chemotherapeutics and radiation therapy when used in combination.11 In human tumour xenograft models in mice, cetuximab and irinotecan synergistically inhibited the growth of orthotopic anaplastic thyroid carcinoma xenografts in vitro and in vivo. Cetuximab potentiated the in vitro anti-proliferative and pro-apoptotic effect of irinotecan and achieved 93% in vivo inhibition of tumour growth when combined with irinotecan, compared to 77% and 79% inhibition when cetuximab and irinotecan were used alone, respectively.5
- Mechanism of action
The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein and a type I receptor tyrosine kinase expressed on both normal and malignant cells. It has been investigated as a therapeutic target for anticancer treatment, as it is often upregulated in cancer types, including head and neck, colon, and rectal cancers.11 When activated by its ligand, EGFR undergoes a conformational change and dimerization to form homodimers or heterodimers with another member of the ErbB family of receptors. Dimerization of EGFR activates the intracellular tyrosine kinase region of EGFR and promotes autophosphorylation, initiating a series of downstream signalling cascades, including cell differentiation, proliferation, migration, angiogenesis, and apoptosis. This EGFR signalling pathway is often dysregulated in cancer cells, leading to aberrant cell growth and enhanced cell survival.12
Cetuximab is a monoclonal antibody that binds specifically to the EGFR on both normal and tumour cells to competitively inhibit the binding of epidermal growth factor (EGF) and other ligands that are produced by normal and tumour tissue epithelial cells.2,11 Upon binding to domain III of EGFR - which is the binding site for its growth factor ligands - cetuximab prevents the receptor from adopting an extended conformation and thereby inhibits EGFR activation, as well as phosphorylation and activation of receptor-associated kinases (MAPK, PI3K/Akt, Jak/Stat).2,8 Inhibition of the EGFR signalling pathway ultimately leads to inhibition of cell cycle progression, cell survival pathways, and tumour cell motility and invasion.3 Cetuximab also induces cell apoptosis and decreases matrix metalloproteinase and vascular endothelial growth factor (VEGF) production.8,11 In vitro, cetuximab was shown to inhibit tumour angiogenesis.5 Binding of cetuximab to EGFR also results in internalization of the antibody-receptor complex, leading to an overall downregulation of EGFR expression.4
K-ras is a small G-protein downstream of EGFR that plays an important role in promoting the EGFR signalling cascade: in some malignant cells, K-ras can acquire activating mutations in exon 2 12 and thus be continuously active regardless of EGFR regulation.11 Since mutant Ras proteins can isolate the pathway from the effect of EGFR, K-Ras mutations can render EGFR inhibitors like cetuximab ineffective in exerting anti-tumour effects.11,12 Cetuximab is thus only limited in its use for K-Ras wild-type, EGFR-expressing cancers.11
Target Actions Organism AEpidermal growth factor receptor binderHumans ULow affinity immunoglobulin gamma Fc region receptor III-B binderHumans UComplement C1q subcomponent subunit A binderHumans UComplement C1q subcomponent subunit B binderHumans UComplement C1q subcomponent subunit C binderHumans ULow affinity immunoglobulin gamma Fc region receptor III-A binderHumans UHigh affinity immunoglobulin gamma Fc receptor I binderHumans ULow affinity immunoglobulin gamma Fc region receptor II-a binderHumans - Absorption
After administration of a 400 mg/m2 initial dose followed by a 250 mg/m2 weekly dose, the steady-state levels of cetuximab was reached by the third weekly infusion with mean peak and trough concentrations across studies ranging from 168 µg/mL to 235 µg/mL and 41 µg/mL to 85 µg/mL, respectively.11 Tmax is about 3 hours.3
- Volume of distribution
The volume of the distribution is about 2-3 L/m2 and is independent of dose.11
- Protein binding
There is no information available.
- Metabolism
Like other monoclonal antibodies, cetuximab is expected to undergo lysosomal degradation by the reticuloendothelial system and protein catabolism by a target‐mediated disposition pathway.6
- Route of elimination
There is limited information available.
- Half-life
After administration of a 400 mg/m2 initial dose followed by a 250 mg/m2 weekly dose, the mean half-life for cetuximab was approximately 112 hours, with a range of 63 to 230 hours.11
- Clearance
In patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck, the estimated clearance rate was 0.103 L/h.7 At doses ranging from 200 to 400 mg/m2, complete saturation of systemic clearance was observed. In a population pharmacokinetic study, female patients had a 25% lower intrinsic cetuximab clearance than male patients, although there was no evidence of the need for dose modification based on sex.3
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
The intravenous LD50 is > 300 mg/kg in mice and > 200 mg/kg in rats.10 There is limited information on the overdose from cetuximab.
In clinical trials, cetuximab was associated with serious and fatal infusion reactions, cardiopulmonary arrest or sudden death, and serious dermatologic toxicities. Pulmonary toxicities, such as interstitial lung disease, interstitial pneumonitis with non-cardiogenic pulmonary edema, and exacerbation of pre-existing fibrotic lung disease have been reported.11
- Pathways
Pathway Category Cetuximab Action Pathway Drug action - Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Low affinity immunoglobulin gamma Fc region receptor II-a --- (T;T) / (C;T) H allelle Effect Directly Studied Patients with this genotype may have increased progression-free survival time when using cetuximab to treat colorectal cancer. Details Low affinity immunoglobulin gamma Fc region receptor III-A --- (T;T) / (G;T) G > T Effect Directly Studied Patients with this genotype have increased progression-free survival time when using cetuximab to treat colorectal cancer. Details
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Cetuximab is combined with Abciximab. Adalimumab The risk or severity of adverse effects can be increased when Cetuximab is combined with Adalimumab. Aducanumab The risk or severity of adverse effects can be increased when Cetuximab is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Cetuximab is combined with Alemtuzumab. Alirocumab The risk or severity of adverse effects can be increased when Cetuximab is combined with Alirocumab. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Erbitux Injection, solution 5 mg/ml Intravenous Merck Ltd. 2016-09-08 Not applicable EU Erbitux Solution 2 mg/1mL Intravenous ImClone LLC 2007-10-02 Not applicable US Erbitux Injection, solution 5 mg/ml Intravenous Merck Ltd. 2016-09-08 Not applicable EU Erbitux Solution 2 mg/1mL Intravenous ImClone LLC 2004-02-12 Not applicable US Erbitux Solution 2 mg / mL Intravenous ImClone LLC 2008-10-28 Not applicable Canada
Categories
- ATC Codes
- L01FE01 — Cetuximab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Cancer immunotherapy
- EGFR (Epidermal Growth Factor Receptor) inhibitors
- Epidermal Growth Factor Receptor Antagonist
- Globulins
- HER1 Antagonists
- Immunoglobulins
- Immunoproteins
- Immunotherapy
- Monoclonal antibodies and antibody drug conjugates
- Narrow Therapeutic Index Drugs
- Proteins
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- PQX0D8J21J
- CAS number
- 205923-56-4
References
- General References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- Wong SF: Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. Clin Ther. 2005 Jun;27(6):684-94. doi: 10.1016/j.clinthera.2005.06.003. [Article]
- Harding J, Burtness B: Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody. Drugs Today (Barc). 2005 Feb;41(2):107-27. doi: 10.1358/dot.2005.41.2.882662. [Article]
- Kim S, Prichard CN, Younes MN, Yazici YD, Jasser SA, Bekele BN, Myers JN: Cetuximab and irinotecan interact synergistically to inhibit the growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice. Clin Cancer Res. 2006 Jan 15;12(2):600-7. doi: 10.1158/1078-0432.CCR-05-1325. [Article]
- Ryman JT, Meibohm B: Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacometrics Syst Pharmacol. 2017 Sep;6(9):576-588. doi: 10.1002/psp4.12224. Epub 2017 Jul 29. [Article]
- Dirks NL, Nolting A, Kovar A, Meibohm B: Population pharmacokinetics of cetuximab in patients with squamous cell carcinoma of the head and neck. J Clin Pharmacol. 2008 Mar;48(3):267-78. doi: 10.1177/0091270007313393. Epub 2008 Jan 24. [Article]
- Vincenzi B, Zoccoli A, Pantano F, Venditti O, Galluzzo S: Cetuximab: from bench to bedside. Curr Cancer Drug Targets. 2010 Feb;10(1):80-95. doi: 10.2174/156800910790980241. [Article]
- Sigismund S, Avanzato D, Lanzetti L: Emerging functions of the EGFR in cancer. Mol Oncol. 2018 Jan;12(1):3-20. doi: 10.1002/1878-0261.12155. Epub 2017 Nov 27. [Article]
- Bristol-Myers Squibb Company: Cetuximab Safety Data Sheet [Link]
- FDA Approved Drug Products: ERBITUX (cetuximab) injection, for intravenous use [Link]
- StatPearls: Cetuximab [Link]
- FDA Approved Drug Products: ERBITUX (cetuximab) injection, for intravenous use [Link]
- External Links
- Genbank
- J00228
- KEGG Drug
- D03455
- PubChem Substance
- 46507042
- 318341
- ChEMBL
- CHEMBL1201577
- Therapeutic Targets Database
- DNC000788
- PharmGKB
- PA10040
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Cetuximab
- FDA label
- Download (73.8 KB)
- MSDS
- Download (84.4 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Colon Rectal Cancer Duke Stage Stageval 1 somestatus stop reason just information to hide Not Available Completed Not Available Colorectal Cancer 2 somestatus stop reason just information to hide Not Available Completed Not Available Colorectal Neoplasms 1 somestatus stop reason just information to hide Not Available Completed Not Available Head And Neck Cancer 3 somestatus stop reason just information to hide Not Available Completed Not Available Metastatic Colorectal Cancer (CRC) 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Cardinal Health
- Catalent Pharma Solutions
- ImClone Systems Inc.
- Oso Biopharmaceuticals Manufacturing LLC
- Dosage Forms
Form Route Strength Injection Intravenous 5 MG/ML Injection, solution Intravenous 5 mg/ml Injection, solution Intravenous; Parenteral 5 MG/ML Solution Intravenous 2 mg/1mL Solution Intravenous 2 mg / mL Solution Intravenous 5.000 mg Solution Intravenous 5 mg Injection, solution Intravenous 100 mg/20ml Injection, solution Intravenous 500 mg/100ml Solution Intravenous 5 mg/ml Solution Intravenous 5 mg/1ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA1340417 No 1999-03-02 2016-03-02 Canada
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 61 °C (FAB fragment), 71 °C (whole mAb) Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000) hydrophobicity -0.413 Not Available isoelectric point 8.48 Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity)
- Specific Function
- actin filament binding
- Gene Name
- EGFR
- Uniprot ID
- P00533
- Uniprot Name
- Epidermal growth factor receptor
- Molecular Weight
- 134276.185 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Harding J, Burtness B: Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody. Drugs Today (Barc). 2005 Feb;41(2):107-27. doi: 10.1358/dot.2005.41.2.882662. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent cytotoxicity and phagocytosis. May serve as a trap for immune complexes in the peripheral circulation which does not activate neutrophils
- Specific Function
- GPI anchor binding
- Gene Name
- FCGR3B
- Uniprot ID
- O75015
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor III-B
- Molecular Weight
- 26242.67 Da
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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes
- Specific Function
- amyloid-beta binding
- Gene Name
- C1QA
- Uniprot ID
- P02745
- Uniprot Name
- Complement C1q subcomponent subunit A
- Molecular Weight
- 26016.47 Da
References
- Deveuve Q, Lajoie L, Barrault B, Thibault G: The Proteolytic Cleavage of Therapeutic Monoclonal Antibody Hinge Region: More Than a Matter of Subclass. Front Immunol. 2020 Feb 11;11:168. doi: 10.3389/fimmu.2020.00168. eCollection 2020. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes
- Specific Function
- Not Available
- Gene Name
- C1QB
- Uniprot ID
- P02746
- Uniprot Name
- Complement C1q subcomponent subunit B
- Molecular Weight
- 26721.62 Da
References
- Deveuve Q, Lajoie L, Barrault B, Thibault G: The Proteolytic Cleavage of Therapeutic Monoclonal Antibody Hinge Region: More Than a Matter of Subclass. Front Immunol. 2020 Feb 11;11:168. doi: 10.3389/fimmu.2020.00168. eCollection 2020. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes
- Specific Function
- Not Available
- Gene Name
- C1QC
- Uniprot ID
- P02747
- Uniprot Name
- Complement C1q subcomponent subunit C
- Molecular Weight
- 25773.56 Da
References
- Deveuve Q, Lajoie L, Barrault B, Thibault G: The Proteolytic Cleavage of Therapeutic Monoclonal Antibody Hinge Region: More Than a Matter of Subclass. Front Immunol. 2020 Feb 11;11:168. doi: 10.3389/fimmu.2020.00168. eCollection 2020. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG). Optimally activated upon binding of clustered antigen-IgG complexes displayed on cell surfaces, triggers lysis of antibody-coated cells, a process known as antibody-dependent cellular cytotoxicity (ADCC). Does not bind free monomeric IgG, thus avoiding inappropriate effector cell activation in the absence of antigenic trigger (PubMed:11711607, PubMed:21768335, PubMed:22023369, PubMed:24412922, PubMed:25786175, PubMed:25816339, PubMed:28652325, PubMed:8609432, PubMed:9242542). Mediates IgG effector functions on natural killer (NK) cells. Binds antigen-IgG complexes generated upon infection and triggers NK cell-dependent cytokine production and degranulation to limit viral load and propagation. Involved in the generation of memory-like adaptive NK cells capable to produce high amounts of IFNG and to efficiently eliminate virus-infected cells via ADCC (PubMed:24412922, PubMed:25786175). Regulates NK cell survival and proliferation, in particular by preventing NK cell progenitor apoptosis (PubMed:29967280, PubMed:9916693). Fc-binding subunit that associates with CD247 and/or FCER1G adapters to form functional signaling complexes. Following the engagement of antigen-IgG complexes, triggers phosphorylation of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters with subsequent activation of phosphatidylinositol 3-kinase signaling and sustained elevation of intracellular calcium that ultimately drive NK cell activation. The ITAM-dependent signaling coupled to receptor phosphorylation by PKC mediates robust intracellular calcium flux that leads to production of pro-inflammatory cytokines, whereas in the absence of receptor phosphorylation it mainly activates phosphatidylinositol 3-kinase signaling leading to cell degranulation (PubMed:1825220, PubMed:23024279, PubMed:2532305). Costimulates NK cells and trigger lysis of target cells independently of IgG binding (PubMed:10318937, PubMed:23006327). Mediates the antitumor activities of therapeutic antibodies. Upon ligation on monocytes triggers TNFA-dependent ADCC of IgG-coated tumor cells (PubMed:27670158). Mediates enhanced ADCC in response to afucosylated IgGs (PubMed:34485821)
- Specific Function
- IgG binding
- Gene Name
- FCGR3A
- Uniprot ID
- P08637
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor III-A
- Molecular Weight
- 29088.895 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses. Mediates IgG effector functions on monocytes triggering antibody-dependent cellular cytotoxicity (ADCC) of virus-infected cells
- Specific Function
- high-affinity IgG receptor activity
- Gene Name
- FCGR1A
- Uniprot ID
- P12314
- Uniprot Name
- High affinity immunoglobulin gamma Fc receptor I
- Molecular Weight
- 42631.525 Da
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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized antigens
- Specific Function
- IgG binding
- Gene Name
- FCGR2A
- Uniprot ID
- P12318
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor II-a
- Molecular Weight
- 35000.42 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at September 05, 2024 06:29