Efalizumab

Identification

Name
Efalizumab
Accession Number
DB00095  (BTD00074, BIOD00074)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Humanized IgG1 kappa isotype monoclonal antibody that binds to human CD11a. Efalizumab has a molecular weight of approximately 150 kilodaltons and is produced in a Chinese hamster ovary mammalian cell expression system in a nutrient medium containing the antibiotic gentamicin.

Protein structure
Db00095
Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
>Heavy Chain Variable Region
EVQLVESGGGLVQPGGSLRLSCAASGYSFTGHWMNWVRQAPGKGLEWVGIMIHPSDSETR
YNQKFKDIRFTISVDKSKNTLYLQMNSLRAEDTAVYYCARIGIYFYGTTYFDYIWGQGTL
VTVSS
>Light Chain Variable Region
DIQMTQSPSSLSASVGDRVTITCRASKTISKYLAWXQQKPGKAPKLLIYSGSTLQSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQHNEYPLTFGQGTKVEIKR
Download FASTA Format
Synonyms
  • anti alphaL integrin
  • antiCD11 alpha
  • hu1124
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RaptivaPowder, for solution150 mgSubcutaneousEmd Serono, A Division Of Emd Inc., Canada2005-10-262009-06-08Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
RaptivaEfalizumab (100 mg/ml)Injection, powder, for solutionSubcutaneousSerono Europe Limited2004-09-202009-08-03Eu
RaptivaEfalizumab (100 mg/ml)Injection, powder, for solutionSubcutaneousSerono Europe Limited2004-09-202009-08-03Eu
RaptivaEfalizumab (100 mg/ml)Injection, powder, for solutionSubcutaneousSerono Europe Limited2004-09-202009-08-03Eu
International/Other Brands
Raptiva
Categories
UNII
XX2MN88N5D
CAS number
214745-43-4

Pharmacology

Indication

For the treatment of adult patients with moderate to severe chronic plaque psoriasis, who are candidates for phototherapy or systemic therapy.

Pharmacodynamics

Lymphocyte activation and trafficking to skin play a role in the pathophysiology of chronic plaque psoriasis. In psoriatic skin, ICAM-1 cell surface expression is upregulated on endothelium and keratinocytes. Raptiva inhibits the binding of LFA-1 to the intercellular adhesion molecule-1 (ICAM-1), thereby inhibiting the adhesion of leukocytes to other cell types.

Mechanism of action

Efalizumab binds to CD11a, a subunit of leukocyte function antigen-1 (LFA-1), which is expressed on all leukocytes. As a result efalizumab decreases cell surface expression of CD11a.

TargetActionsOrganism
AIntegrin alpha-L
antibody
Human
ULow affinity immunoglobulin gamma Fc region receptor III-BNot AvailableHuman
UComplement C1r subcomponentNot AvailableHuman
UComplement C1q subcomponent subunit ANot AvailableHuman
UComplement C1q subcomponent subunit BNot AvailableHuman
UComplement C1q subcomponent subunit CNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor III-ANot AvailableHuman
UHigh affinity immunoglobulin gamma Fc receptor INot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-aNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-bNot AvailableHuman
ULow affinity immunoglobulin gamma Fc region receptor II-cNot AvailableHuman
Absorption

Average efalizumab bioavailability following subcutaneous administration was estimated at 30 to 50%.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

5 days

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Efalizumab is combined with 2-Methoxyethanol.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Efalizumab is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbataceptThe risk or severity of adverse effects can be increased when Efalizumab is combined with Abatacept.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Efalizumab.
AbetimusThe risk or severity of adverse effects can be increased when Efalizumab is combined with Abetimus.
AbituzumabThe risk or severity of adverse effects can be increased when Efalizumab is combined with Abituzumab.
ActeosideThe risk or severity of adverse effects can be increased when Efalizumab is combined with Acteoside.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Efalizumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Efalizumab is combined with Adecatumumab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Efalizumab.
Food Interactions
Not Available

References

General References
  1. Werther WA, Gonzalez TN, O'Connor SJ, McCabe S, Chan B, Hotaling T, Champe M, Fox JA, Jardieu PM, Berman PW, Presta LG: Humanization of an anti-lymphocyte function-associated antigen (LFA)-1 monoclonal antibody and reengineering of the humanized antibody for binding to rhesus LFA-1. J Immunol. 1996 Dec 1;157(11):4986-95. [PubMed:8943405]
  2. Descamps V: [Efalizumab]. Ann Dermatol Venereol. 2006 Aug-Sep;133(8-9 Pt 1):666-78. [PubMed:17053736]
External Links
PubChem Substance
46505252
ChEMBL
CHEMBL1201575
Therapeutic Targets Database
DAP001095
PharmGKB
PA164748817
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Efalizumab
ATC Codes
L04AA21 — Efalizumab
FDA label
Download (1.45 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAtopic Dermatitis (AD)1
1CompletedTreatmentHidradenitis Suppurativa (HS)1
1CompletedTreatmentMacular Edema (ME) / Uveitis1
1CompletedTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
1CompletedTreatmentPsoriatic Arthritis1
1WithdrawnTreatmentAge Related Macular Degeneration (ARMD) / AMD / CNV1
1WithdrawnTreatmentDiabetic Macular Edema (DME)1
1, 2CompletedTreatmentPsoriasis1
1, 2TerminatedTreatmentChronic Renal Failure (CRF) / Transplantation, Kidney1
1, 2TerminatedTreatmentDiabetes, Diabetes Mellitus Type 1 / Hypoglycemia1
1, 2WithdrawnNot AvailableAutoimmune Diseases1
2CompletedTreatmentAtopic Dermatitis (AD)1
2CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
2CompletedTreatmentRheumatoid Arthritis1
2TerminatedTreatmentDiscoid Lupus Erthematosus of the Scalp1
2TerminatedTreatmentSjögren's Syndrome1
2WithdrawnTreatmentAlopecia Totalis (AT)1
2WithdrawnTreatmentDiabetes, Diabetes Mellitus Type 11
2, 3WithdrawnTreatmentTransplantation, Kidney1
3CompletedTreatmentPsoriasis5
3CompletedTreatmentPsoriasis, Moderate to Severe2
4CompletedTreatmentPsoriasis5
4CompletedTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
4TerminatedNot AvailablePsoriasis Vulgaris (Plaque Psoriasis)1
4TerminatedTreatmentChronic Plaque Psoriasis3
Not AvailableCompletedTreatmentLichen Planus, Oral1
Not AvailableTerminatedSupportive CareGraft Versus Host Disease (GVHD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Genentech Inc.
Dosage forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous100 mg/ml
Powder, for solutionSubcutaneous150 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)

Taxonomy

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

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antibody
General Function
Metal ion binding
Specific Function
Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated ...
Gene Name
ITGAL
Uniprot ID
P20701
Uniprot Name
Integrin alpha-L
Molecular Weight
128768.495 Da
References
  1. Frampton JE, Plosker GL: Efalizumab: a review of its use in the management of chronic moderate-to-severe plaque psoriasis. Am J Clin Dermatol. 2009;10(1):51-72. doi: 10.2165/0128071-200910010-00009. [PubMed:19170413]
  2. Descamps V: [Efalizumab]. Ann Dermatol Venereol. 2006 Aug-Sep;133(8-9 Pt 1):666-78. [PubMed:17053736]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific 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...
Gene Name
FCGR3B
Uniprot ID
O75015
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-B
Molecular Weight
26215.64 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type peptidase activity
Specific Function
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.
Gene Name
C1R
Uniprot ID
P00736
Uniprot Name
Complement C1r subcomponent
Molecular Weight
80118.04 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific 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) proe...
Gene Name
C1QA
Uniprot ID
P02745
Uniprot Name
Complement C1q subcomponent subunit A
Molecular Weight
26016.47 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific 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) proe...
Gene Name
C1QB
Uniprot ID
P02746
Uniprot Name
Complement C1q subcomponent subunit B
Molecular Weight
26721.62 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific 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) proe...
Gene Name
C1QC
Uniprot ID
P02747
Uniprot Name
Complement C1q subcomponent subunit C
Molecular Weight
25773.56 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
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...
Gene Name
FCGR3A
Uniprot ID
P08637
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor III-A
Molecular Weight
29088.895 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor signaling protein activity
Specific Function
High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.
Gene Name
FCGR1A
Uniprot ID
P12314
Uniprot Name
High affinity immunoglobulin gamma Fc receptor I
Molecular Weight
42631.525 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific 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 ...
Gene Name
FCGR2A
Uniprot ID
P12318
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-a
Molecular Weight
35000.42 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
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 complex...
Gene Name
FCGR2B
Uniprot ID
P31994
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-b
Molecular Weight
34043.355 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane signaling receptor activity
Specific Function
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 modulat...
Gene Name
FCGR2C
Uniprot ID
P31995
Uniprot Name
Low affinity immunoglobulin gamma Fc region receptor II-c
Molecular Weight
35577.96 Da
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:17139284]
  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:17016423]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2018 19:14