DrugBank: Omalizumab (DB00043)

targets (2)

Identification

Name

Omalizumab

Accession Number

DB00043 (BIOD00081, BTD00081)

Type

biotech

Groups

approved

Description

A recombinant DNA-derived humanized IgG1k monoclonal antibody that selectively binds to human immunoglobulin E (IgE). Xolair is produced by a Chinese hamster ovary cell suspension culture in a nutrient medium containing the antibiotic gentamicin.

Protein structure

Display: 3D Structure

Protein chemical formula

C₆₄₅₀H₉₉₁₆N₁₇₁₄O₂₀₂₃S₃₈

Protein average weight

145058.2000

Sequences

>Anti IgE antibody VH domain chain 1
EVQLVESGGGLVQPGGSLRLSCAVSGYSITSGYSWNWIRQAPGKGLEWVASITYDGSTNY
ADSVKGRFTISRDDSKNTFYLQMNSLRAEDTAVYYCARGSHYFGHWHFAVWGQGTLVTVS
SGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGK

>Anti IgE antibody VL domain chain 1
DIQLTQSPSSLSASVGDRVTITCRASQSVDYDGDSYMNWYQQKPGKAPKLLIYAASYLES
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHEDPYTFGQGTKVEIKRTVAAPSVF
IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS
STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR

>Anti IgE antibody VH domain chain 2
EVQLVESGGGLVQPGGSLRLSCAVSGYSITSGYSWNWIRQAPGKGLEWVASITYDGSTNY
ADSVKGRFTISRDDSKNTFYLQMNSLRAEDTAVYYCARGSHYFGHWHFAVWGQGTLVTVS
SGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGK

>Anti IgE antibody VL domain chain 2
DIQLTQSPSSLSASVGDRVTITCRASQSVDYDGDSYMNWYQQKPGKAPKLLIYAASYLES
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHEDPYTFGQGTKVEIKRTVAAPSVF
IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS
STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR

FASTA

Synonyms

Ig gamma-1 chain C region

Salts

Not Available

Brand names

Name	Company
Xolair (Genentech Inc)

Brand mixtures

Not Available

Categories

Immunomodulatory Agents
Anti-Asthmatic Agents

CAS number

242138-07-4

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

For treatment of asthma caused by allergies

Pharmacodynamics

Xolair inhibits the binding of IgE to the high-affinity IgE receptor (FceRI) on the surface of mast cells and basophils. Reduction in surface-bound IgE on FceRI-bearing cells limits the degree of release of mediators of the allergic response. Xolair is used to treat severe, persisten asthma.

Mechanism of action

Xolair binds to IgE (a class of antibodies normally secreted in allergic responses), which prevents their binding to mast cells and basophils.

Absorption

Not Available

Volume of distribution

78 ± 32 mL/kg

Protein binding

Not Available

Metabolism

Most likely removed by opsonization via the reticuloendothelial system.

Route of elimination

Liver elimination of IgG includes degradation in the liver reticuloendothelial system (RES) and endothelial cells. Intact IgG is also excreted in bile.

Half life

26 days

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Dosage forms

Form	Route	Strength
Powder, for solution	Subcutaneous

Prices

Unit description	Cost	Unit
Xolair 150 mg vial	715.42 USD	vial

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Country	Patent Number	Approved	Expires (estimated)
Canada	2113813	2005-04-12	2012-08-14
Canada	1340233	1998-12-15	2015-12-15

Properties

State

liquid

Experimental Properties

Property	Value	Source
melting point	61 °C (FAB fragment), 71 °C (whole mAb)	Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
hydrophobicity	-0.432	Not Available
isoelectric point	7.03	Not Available

References

Synthesis Reference

Not Available

General Reference

Karagiannis SN, Wang Q, East N, Burke F, Riffard S, Bracher MG, Thompson RG, Durham SR, Schwartz LB, Balkwill FR, Gould HJ: Activity of human monocytes in IgE antibody-dependent surveillance and killing of ovarian tumor cells. Eur J Immunol. 2003 Apr;33(4):1030-40. Pubmed

External Links

Resource	Link
UniProt	P01857
Genbank	J00228
PharmGKB	PA164752253
Drug Product Database	2260565
RxList	http://www.rxlist.com/cgi/generic/xolair.htm
Drugs.com	http://www.drugs.com/cdi/omalizumab.html
Wikipedia	http://en.wikipedia.org/wiki/Omalizumab

ATC Codes

R03DX05

AHFS Codes

48:92.00

PDB Entries

1IGT

FDA label

show (53.5 KB)

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. High affinity immunoglobulin epsilon receptor subunit alpha Pharmacological action: yes Binds to the Fc region of immunoglobulins epsilon. High affinity receptor. Responsible for initiating the allergic response. Binding of allergen to receptor-bound IgE leads to cell activation and the release of mediators (such as histamine) responsible for the manifestations of allergy. The same receptor also induces the secretion of important lymphokines Organism class: human UniProt ID: P12319 Gene: FCER1A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Beck LA, Marcotte GV, MacGlashan D, Togias A, Saini S: Omalizumab-induced reductions in mast cell Fce psilon RI expression and function. J Allergy Clin Immunol. 2004 Sep;114(3):527-30. Pubmed Mirkina I, Schweighoffer T, Kricek F: Inhibition of human cord blood-derived mast cell responses by anti-Fc epsilon RI mAb 15/1 versus anti-IgE Omalizumab. Immunol Lett. 2007 Apr 15;109(2):120-8. Epub 2007 Mar 1. Pubmed 2. High affinity immunoglobulin epsilon receptor subunit beta Pharmacological action: yes Actions: antagonist Binds to the Fc region of immunoglobulins epsilon. High affinity receptor. Responsible for initiating the allergic response. Binding of allergen to receptor-bound IgE leads to cell activation and the release of mediators (such as histamine) responsible for the manifestations of allergy. The same receptor also induces the secretion of important lymphokines Organism class: human UniProt ID: Q01362 Gene: MS4A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report 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 DuBuske LM: IgE, allergic diseases, and omalizumab. Curr Pharm Des. 2006;12(30):3929-44. Pubmed

Targets

1. High affinity immunoglobulin epsilon receptor subunit alpha

Pharmacological action: yes

Binds to the Fc region of immunoglobulins epsilon. High affinity receptor. Responsible for initiating the allergic response. Binding of allergen to receptor-bound IgE leads to cell activation and the release of mediators (such as histamine) responsible for the manifestations of allergy. The same receptor also induces the secretion of important lymphokines

Organism class: human
UniProt ID: P12319 Link_out

Gene: FCER1A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Beck LA, Marcotte GV, MacGlashan D, Togias A, Saini S: Omalizumab-induced reductions in mast cell Fce psilon RI expression and function. J Allergy Clin Immunol. 2004 Sep;114(3):527-30. Pubmed
Mirkina I, Schweighoffer T, Kricek F: Inhibition of human cord blood-derived mast cell responses by anti-Fc epsilon RI mAb 15/1 versus anti-IgE Omalizumab. Immunol Lett. 2007 Apr 15;109(2):120-8. Epub 2007 Mar 1. Pubmed

2. High affinity immunoglobulin epsilon receptor subunit beta

Pharmacological action: yes
Actions: antagonist

Organism class: human
UniProt ID: Q01362 Link_out

Gene: MS4A2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
DuBuske LM: IgE, allergic diseases, and omalizumab. Curr Pharm Des. 2006;12(30):3929-44. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on November 13, 2010 09:04