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Identification
Name Bevacizumab
Accession Number DB00112 (BIOD00087, BTD00087)
Type biotech
Groups approved
Description

A recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor (VEGF). Bevacizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to VEGF. Bevacizumab is produced in a Chinese Hamster Ovary mammalian cell expression system in a nutrient medium containing the antibiotic gentamicin and has a molecular weight of approximately 149 kilodaltons.
Protein structure Db00112
Display: 3D Structure
Protein chemical formula Not Available
Protein average weight Not Available
Sequences 
>1bj1_H|Fab-12, F(ab)-12, 12-IgG1, rhuMAb-VEGF|||VH-CH1 (VH(1-123)+CH1(124-215))|||||||231||||MW 24867.8|MW 24867.8|
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVGWINTYTGEPTY
AADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKYPHYYGSSHWYFDVWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT

>1bj1_L|Fab-12, F(ab)-12, 12-IgG1, rhuMAb-VEGF|||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(108-213))|||||||214||||MW 23451.0|MW 23451.0|
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTSSLHSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>1bj1_J|Fab-12, F(ab)-12, 12-IgG1, rhuMAb-VEGF|||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(108-213))|||||||214||||MW 23451.0|MW 23451.0|
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTSSLHSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>1bj1_K|Fab-12, F(ab)-12, 12-IgG1, rhuMAb-VEGF|||VH-CH1 (VH(1-123)+CH1(124-215))|||||||231||||MW 24867.8|MW 24867.8|
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVGWINTYTGEPTY
AADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKYPHYYGSSHWYFDVWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT

FASTA
Synonyms
  • antiVEGF
  • Avastin
  • bevacizumab
  • R-435
Brand names
  • Avastin
  • Avastin (Genentech Inc)
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents
  • Antiangiogenesis Agents
CAS number 216974-75-3
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication As part of combination therapy for metastatic colorectal cancer and HER2-negative metastatic breast cancer.
Pharmacodynamics Bevacizumab prevents or reduces the formation of blood vessels (angiogenesis) thereby preventing or reducing metatstatic disease progressing. Bevacizumab binds VEGF and prevents vascular endothelial growth and endothelial cell proliferation.
Mechanism of action Bevacizumab binds VEGF and prevents the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. This prevents blood vessel proliferation and tumour metastasis.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Most likely removed by opsonization via the reticuloendothelial system when bound to endothelial cells, or by human antimurine antibody production
Route of elimination Not Available
Half life Not Available
Clearance
  • 0.26 L/day [Male patients who received 1 to 20 mg/kg of Avastin weekly, every 2 weeks, or every 3 weeks]
  • 0.21 L/day [Female patients who received 1 to 20 mg/kg of Avastin weekly, every 2 weeks, or every 3 weeks]
  • 0.25 L/day [Patients with higher tumor burden who received 1 to 20 mg/kg of Avastin weekly, every 2 weeks, or every 3 weeks]
  • 0.2 L/day [patients with tumor burdens below the median who received 1 to 20 mg/kg of Avastin weekly, every 2 weeks, or every 3 weeks]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00420 Bevacizumab Pathway SMP00420
Pharmacoeconomics
Manufacturers
  • Roche Pharmaceuticals
Packagers
Dosage forms
Form Route Strength
Solution Intravenous
Prices
Unit description Cost Unit
Avastin 400 mg/16ml Solution 16ml Vial 2786.78 USD vial
Avastin 100 mg/4ml Solution 4ml Vial 696.7 USD vial
Avastin 100 mg/4 ml vial 167.48 USD ml
Patents
Country Patent Number Approved Expires
Canada 2286330 2008-06-10 2018-04-03
Canada 2145985 2003-09-16 2012-10-28
Properties
State liquid
Melting point 61 oC (FAB fragment), 71 oC (whole mAb) - Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000).
Experimental Properties Not Available
References
Synthesis Reference Not Available
General Reference
  1. Velcheti V, Viswanathan A, Govindan R: The proportion of patients with metastatic non-small cell lung cancer potentially eligible for treatment with bevacizumab: a single institutional survey. J Thorac Oncol. 2006 Jun;1(5):501. Pubmed
  2. IMGT Link
External Links
Resource Link
PharmGKB PA13023299 Link_out
Drug Product Database 2270994 Link_out
RxList http://www.rxlist.com/cgi/generic3/avastin.htm Link_out
Drugs.com http://www.drugs.com/cdi/bevacizumab-solution.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Bevacizumab Link_out
ATC Codes
  • L01XC07
AHFS Codes
  • 10:00.00
PDB Entries
FDA label show (133.3 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Vascular endothelial growth factor A

Pharmacological action: yes

Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis, and induces permeabilization of blood vessels. Binds to the VEGFR1/Flt-1 and VEGFR2/Kdr receptors, heparan sulfate and heparin. Neuropilin-1 binds isoforms VEGF-165 and VEGF-145

Organism class: human
UniProt ID: P15692 Link_out
Gene: VEGF Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Gerber HP, Ferrara N: Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005 Feb 1;65(3):671-80. Pubmed

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

Pharmacological action: unknown

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

Organism class: human
UniProt ID: O75015 Link_out
Gene: FCGR3B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Complement C1r subcomponent

Pharmacological action: unknown

C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system

Organism class: human
UniProt ID: P00736 Link_out
Gene: C1R Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

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

Organism class: human
UniProt ID: P02745 Link_out
Gene: C1QA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

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

Organism class: human
UniProt ID: P02746 Link_out
Gene: C1QB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

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

Organism class: human
UniProt ID: P02747 Link_out
Gene: C1QC Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis

Organism class: human
UniProt ID: P08637 Link_out
Gene: FCGR3A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

8. High affinity immunoglobulin gamma Fc receptor I

Pharmacological action: unknown

Binds to the Fc region of immunoglobulins gamma. High affinity receptor

Organism class: human
UniProt ID: P12314 Link_out
Gene: FCGR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Low affinity immunoglobulin gamma Fc region receptor II-a

Pharmacological action: unknown

Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens

Organism class: human
UniProt ID: P12318 Link_out
Gene: FCGR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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

Pharmacological action: unknown

Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B- cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis

Organism class: human
UniProt ID: P31994 Link_out
Gene: FCGR2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

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

Pharmacological action: unknown

Receptor for the Fc region of complexed immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells

Organism class: human
UniProt ID: P31995 Link_out
Gene: FCGR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on September 29, 2010 14:34

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.