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Namespace Prefixes

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Statements

Subject Item
n2:DB06681
rdf:type
n3:Drug
n3:description
Belatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. It is approved for the treatment of rheumatoid arthritis. Belatacept selectively blocks the process of T-cell activation. It was developed by Bristol-Myers-Squibb. It differs from abatacept (Orencia) by only 2 amino acids. FDA approved on June 15, 2011.
n3:dosage
n5:271B4DF5-363D-11E5-9242-09173F13E4C5
n3:generalReferences
# Wekerle T, Grinyo JM: Belatacept: from rational design to clinical application. Transpl Int. 2012 Feb;25(2):139-50. doi: 10.1111/j.1432-2277.2011.01386.x. Epub 2011 Dec 7. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/22151353 # Garnock-Jones KP: Belatacept: in adult kidney transplant recipients. BioDrugs. 2012 Dec 1;26(6):413-24. doi: 10.2165/11208900-000000000-00000. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/22928660 # Garnock-Jones KP: Belatacept: in adult kidney transplant recipients. BioDrugs. 2012 Dec 1;26(6):413-24. doi: 10.2165/11208900-000000000-00000. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/22928660
n3:group
approved
n3:halfLife
Mean terminal elimination half-life: 10 mg/kg, kidney transplant recipients= 9.8 days; 5 mg/kg, kidney transplant recipient = 8.2 days
n3:indication
For prophylaxis of organ rejection. It is also used concomitantly with basiliximumab for induction therapy, mycophenolate, and corticosteriods in kidney transplant recepients that are seropositive for the Epstein-Barr virus.
owl:sameAs
n16:DB06681
dcterms:title
Belatacept
adms:identifier
n12:DB06681 n14:Belatacept n17:D03222 n18:0003-0371-13
n3:mechanismOfAction
Belatacept is a fusion protein in which the Fc portion of human IgG1 is attached onto the extracellular portion of human CTLA-4 (CD152). Belatacept specifically binds to CD80 and CD86 receptors that are found on the antigen-presenting cell (B cells, macrophages, dendritic cells) to block selective T-cell lymphocyte costimulation. CD80 and CD86 would normally act as the ligands to the CD28 receptor T-cells in which this interaction triggers the activation of T lymphocytes. However in the presence of belatacept, because the extracellular CTLA-4 component binds to CD28 with higher affinity than CD80 or CD86, T lymphyocyte anergy, a state of antigen specific tolerance, occurs instead. The T cell is also no longer able to respond to their antigen.
n3:synonym
LEA 29Y BMS224818 BMS-224818 CTLA4-Ig CD152 antigen LEA29Y
n3:volumeOfDistribution
Vd, steady state, transplant patients, 10 mg/kg = 0.11 L/kg; Vd, steady state, transplant patients, 5 mg/kg = 0.12 L/kg
n7:hasAHFSCode
n8:92-44
foaf:page
n10:nulojix-drug.htm n13:belatacept.html
n3:Molecular-Formula
n4:271B4DF7-363D-11E5-9242-09173F13E4C5
n3:Molecular-Weight
n4:271B4DF6-363D-11E5-9242-09173F13E4C5
n7:hasATCCode
n19:L04AA28
n3:absorption
Following multiple intravenous doses of an initial 10 mg/kg dose and followed by a maintenance dose of 5 mg/kg in kidney transplant recipients, these are the following pharmacokinetic parameters: Cmax, 10 mg/kg = 247 µg/mL; Cmax, 5 mg/kg = 139 µg/mL; AUC, 10 mg/kg = 22,252 µg · h/mL; AUC, 5 mg/kg = 14,090 µg · h/mL; Belatacept had linear and dose-dependent pharmacokinetic profile.
n3:affectedOrganism
Humans and other mammals
n3:casRegistryNumber
706808-37-9
n3:category
n3:clearance
Increased body weight may increase the clearance rate of belatacept. Mean systemic clearance: 10 mg/kg, kidney transplant recipients= 0.49 mL/h/kg; 5 mg/kg, kidney transplant recipient = 0.51 mL/h/kg.