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Identification
NameAlefacept
Accession NumberDB00092  (BTD00055, BIOD00055)
TypeBiotech
GroupsApproved, Withdrawn
DescriptionImmunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) linked to the Fc (hinge, CH2 and CH3 domains) portion of human IgG1. Produced by CHO cells, mW is 91.4 kD.
Protein structureDb00092
Related Articles
Protein chemical formulaC2306H3594N610O694S26
Protein average weight51801.1 Da
Sequences
>Alefacept heavy chain 
CFSQQIYGVVYGNVTFHVPSNVPLKEVLWKKQKDKVAELENSEFRAFSSFKNRVYLDTVS
GSLTIYNLTSSDEDEYEMESPNITDTMKFFLYVLESLPSPTLTCALTNGSIEVQCMIPEH
YNSHRGLIMYSWDCPMEQCKRNSTSIYFKMENDLPQKIQCTLSNPLFNTTSSIILTTCIP
SSGHSRHRYALIPIPLAVITTCIVLYMNGILKCDRKPDRTNSNRVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPQVKFNWYVDGVQVHNAKTK
PREQQYNSTYRVVSVLTVLHQNWLDGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Alefacept light chain
MVAGSDAGRALGVLSVVCLLHCFGFISCFSQQIYGVVYGNVTFHVPSNVPLKEVLWKKQK
DKVAELENSEFRAFSSFKNRVYLDTVSGSLTIYNLTSSDEDEYEMESPNITDTMKFFLYV
LESLPSPTLTCALTNGSIEVQCMIPEHYNSHRGLIMYSWDCPMEQCKRNSTSIYFKMEND
LPQKIQCTLSNPLFNTTSSIILTTCIPSSGHSRHRYALIPIPLAVITTCIVLYMNGILKC
DRKPDRTNSN
Download FASTA Format
Synonyms
ASP0485
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmevivePowder, for solution15 mgIntramuscularAstellas Pharma Canada Inc2004-10-122012-12-01Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIELK3V90G6C
CAS number222535-22-0
Pharmacology
IndicationAs an immunosuppressive drug, Alefacept can be used for treatment of moderate to severe chronic plaque psoriasis
Structured Indications Not Available
PharmacodynamicsInterferes with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Activation of T lymphocytes involving the interaction between LFA-3 on antigen-presenting cells and CD2 on T lymphocytes plays a role in the pathophysiology of chronic plaque psoriasis. Also causes a reduction in subsets of CD2+ T lymphocytes as well as CD4+ and CD8+ T lymphocytes.
Mechanism of actionInhibits T-lymphocyte activation and production by binding to the CD2 lymphocyte antigen.
TargetKindPharmacological actionActionsOrganismUniProt ID
T-cell surface antigen CD2Proteinyes
inhibitor
HumanP06729 details
Complement C1r subcomponentProteinunknownNot AvailableHumanP00736 details
Complement C1q subcomponent subunit AProteinunknownNot AvailableHumanP02745 details
Complement C1q subcomponent subunit BProteinunknownNot AvailableHumanP02746 details
Complement C1q subcomponent subunit CProteinunknownNot AvailableHumanP02747 details
Low affinity immunoglobulin gamma Fc region receptor III-AProteinunknownNot AvailableHumanP08637 details
High affinity immunoglobulin gamma Fc receptor IProteinunknownNot AvailableHumanP12314 details
Low affinity immunoglobulin gamma Fc region receptor II-aProteinunknownNot AvailableHumanP12318 details
Low affinity immunoglobulin gamma Fc region receptor II-bProteinunknownNot AvailableHumanP31994 details
Low affinity immunoglobulin gamma Fc region receptor II-cProteinunknownNot AvailableHumanP31995 details
Low affinity immunoglobulin gamma Fc region receptor III-BProteinunknownNot AvailableHumanO75015 details
Related Articles
AbsorptionBioavailability after IM administration is 63%.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life~270 hours
ClearanceNot Available
ToxicityWhile it has been found to cross the placenta in monkeys, it is not yet known if it also diffuses into breast milk.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
ALT-110The risk or severity of adverse effects can be increased when Alefacept is combined with ALT-110.Investigational
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Alefacept.Investigational
CDX-110The risk or severity of adverse effects can be increased when Alefacept is combined with CDX-110.Investigational
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Alefacept.Approved
FingolimodAlefacept may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe risk or severity of adverse effects can be increased when Alefacept is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Alefacept is combined with GI-5005.Investigational
INGN 201The risk or severity of adverse effects can be increased when Alefacept is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Alefacept is combined with INGN 225.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Alefacept is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Alefacept is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Alefacept.Approved, Investigational
Rabies vaccineThe risk or severity of adverse effects can be increased when Alefacept is combined with Rabies vaccine.Approved
Rabies vaccineThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Alefacept.Approved
RoflumilastRoflumilast may increase the immunosuppressive activities of Alefacept.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Alefacept.Approved
SRP 299The risk or severity of adverse effects can be increased when Alefacept is combined with SRP 299.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Alefacept.Approved, Investigational
TG4010The risk or severity of adverse effects can be increased when Alefacept is combined with TG4010.Investigational
TofacitinibAlefacept may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Alefacept.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Koo JY, Bagel J, Sweetser MT, Ticho BS: Alefacept in combination with ultraviolet B phototherapy for the treatment of chronic plaque psoriasis: results from an open-label, multicenter study. J Drugs Dermatol. 2006 Jul-Aug;5(7):623-8. [PubMed:16865867 ]
  2. Krell JM: Use of alefacept and etanercept in 3 patients whose psoriasis failed to respond to etanercept. J Am Acad Dermatol. 2006 Jun;54(6):1099-101. [PubMed:16713481 ]
  3. Parrish CA, Sobera JO, Robbins CM, Cantrell WC, Desmond RA, Elewski BE: Alefacept in the treatment of psoriatic nail disease: a proof of concept study. J Drugs Dermatol. 2006 Apr;5(4):339-40. [PubMed:16673801 ]
  4. Link [Link]
External Links
ATC CodesL04AA15
AHFS Codes
  • 84:92.00
PDB Entries
FDA labelNot Available
MSDSNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntramuscular15 mg
Prices
Unit descriptionCostUnit
Amevive 15 mg vial1190.4USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.432Not Available
isoelectric point7.86Not Available
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Receptor binding
Specific Function:
CD2 interacts with lymphocyte function-associated antigen (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytoplasmic domain is implicated in the signaling function.
Gene Name:
CD2
Uniprot ID:
P06729
Molecular Weight:
39447.96 Da
References
  1. Chamian F, Lin SL, Lee E, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG, Lowes MA: Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis. J Transl Med. 2007 Jun 7;5:27. [PubMed:17555598 ]
  2. da Silva AJ, Brickelmaier M, Majeau GR, Li Z, Su L, Hsu YM, Hochman PS: Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J Immunol. 2002 May 1;168(9):4462-71. [PubMed:11970990 ]
  3. Larsen R, Ryder LP, Svejgaard A, Gniadecki R: Changes in circulating lymphocyte subpopulations following administration of the leucocyte function-associated antigen-3 (LFA-3)/IgG1 fusion protein alefacept. Clin Exp Immunol. 2007 Jul;149(1):23-30. Epub 2007 Apr 2. [PubMed:17403057 ]
  4. Goedkoop AY, de Rie MA, Picavet DI, Kraan MC, Dinant HJ, van Kuijk AW, Tak PP, Bos JD, Teunissen MB: Alefacept therapy reduces the effector T-cell population in lesional psoriatic epidermis. Arch Dermatol Res. 2004 Apr;295(11):465-73. Epub 2004 Feb 14. [PubMed:14968366 ]
  5. Ortonne JP: Clinical response to alefacept: results of a phase 3 study of intramuscular administration of alefacept in patients with chronic plaque psoriasis. J Eur Acad Dermatol Venereol. 2003 Jul;17 Suppl 2:12-6. [PubMed:12795770 ]
  6. 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:
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
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) 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.
Gene Name:
C1QA
Uniprot ID:
P02745
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) 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.
Gene Name:
C1QB
Uniprot ID:
P02746
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) 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.
Gene Name:
C1QC
Uniprot ID:
P02747
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 phagocytosis.
Gene Name:
FCGR3A
Uniprot ID:
P08637
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 ]
  3. da Silva AJ, Brickelmaier M, Majeau GR, Li Z, Su L, Hsu YM, Hochman PS: Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J Immunol. 2002 May 1;168(9):4462-71. [PubMed:11970990 ]
  4. Vaishnaw AK, TenHoor CN: Pharmacokinetics, biologic activity, and tolerability of alefacept by intravenous and intramuscular administration. J Pharmacokinet Pharmacodyn. 2002 Dec;29(5-6):415-26. [PubMed:12795239 ]
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
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 antigens.
Gene Name:
FCGR2A
Uniprot ID:
P12318
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 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 ...
Gene Name:
FCGR2B
Uniprot ID:
P31994
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 modulation of antibody production by B-cells.
Gene Name:
FCGR2C
Uniprot ID:
P31995
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 ]
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 cytotoxicity and phagocytosis. May serve as a trap for immune complexes in the peripheral circulation which does not activate neutrophils.
Gene Name:
FCGR3B
Uniprot ID:
O75015
Molecular Weight:
26215.64 Da
References
  1. da Silva AJ, Brickelmaier M, Majeau GR, Li Z, Su L, Hsu YM, Hochman PS: Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J Immunol. 2002 May 1;168(9):4462-71. [PubMed:11970990 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23