Identification
NameBelatacept
Accession NumberDB06681
TypeBiotech
GroupsApproved
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.

Protein structureNo structure small
Related Articles
Protein chemical formulaC3508H5440N922O1096S32
Protein average weight92300.0 Da (with glycosylation)
Sequences
> sequence for belatacept
MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAATYMMGNELTF
LDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYEGIGNGTQIYVIDPEPC
PDSDQEPKSSDKTHTSPPSPAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED
PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA
PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format
SynonymsNot Available
External IDs BMS-224818 / BMS224818
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NulojixInjection, powder, for solution250 mgIntravenousBristol Myers Squibb Pharma Eeig2011-06-17Not applicableEu
NulojixInjection, powder, for solution250 mgIntravenousBristol Myers Squibb Pharma Eeig2011-06-17Not applicableEu
NulojixInjection, powder, lyophilized, for solution250 mg/1IntravenousE.R. Squibb & Sons, L.L.C.2011-06-15Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIE3B2GI648A
CAS number706808-37-9
Pharmacology
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.

Structured Indications
Pharmacodynamics

Belatacept binds to CD86 with a 4-fold higher affinity than abatacept. It also binds to CD80 with a 2-fold higher affinity than abatacept. It was observed in non-human primates that belatacept prolongs graft survival due to a decrease in antibody production against the donor organ. Furthermore, belatacept also inhibits the primary humoral immune response which is indicated by the decrease in post-transplant levels of IgG, IgM, and IgA. The magnitude of this effect is more significant in belatacept than it is in cyclosporine.

Mechanism of action

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.

TargetKindPharmacological actionActionsOrganismUniProt ID
T-lymphocyte activation antigen CD86ProteinunknownNot AvailableHumanP42081 details
T-lymphocyte activation antigen CD80ProteinunknownNot AvailableHumanP33681 details
Related Articles
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.

Volume of distribution

Vd, steady state, transplant patients, 10 mg/kg = 0.11 L/kg; Vd, steady state, transplant patients, 5 mg/kg = 0.12 L/kg

Protein bindingNot Available
Metabolism

The cytochrome P450 enzyme system or uridine diphosphate-glucuronosyltransferases are not expected to be involved with the metabolism of belatacept. Because the drug is a protein, belatacept is degraded into smaller peptides and amino acids by proteolytic enzymes.

Route of eliminationNot Available
Half life

Mean terminal elimination half-life: 10 mg/kg, kidney transplant recipients= 9.8 days; 5 mg/kg, kidney transplant recipient = 8.2 days

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.

ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Belatacept.Investigational
BelimumabThe risk or severity of adverse effects can be increased when Belatacept is combined with Belimumab.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Belatacept.Approved
FingolimodBelatacept may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe risk or severity of adverse effects can be increased when Belatacept is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Belatacept is combined with GI-5005.Investigational
INGN 201The risk or severity of adverse effects can be increased when Belatacept is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Belatacept is combined with INGN 225.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Belatacept is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Belatacept is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Belatacept.Approved, Investigational
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Belatacept is combined with Rabies vaccine.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Belatacept.Approved
RindopepimutThe risk or severity of adverse effects can be increased when Belatacept is combined with CDX-110.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Belatacept.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Belatacept.Approved
SRP 299The risk or severity of adverse effects can be increased when Belatacept is combined with SRP 299.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Belatacept.Approved, Investigational
TG4010The risk or severity of adverse effects can be increased when Belatacept is combined with TG4010.Investigational
TofacitinibBelatacept may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Belatacept.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. 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:22151353 ]
  2. Garnock-Jones KP: Belatacept: in adult kidney transplant recipients. BioDrugs. 2012 Dec 1;26(6):413-24. doi: 10.2165/11208900-000000000-00000. [PubMed:22928660 ]
External Links
ATC CodesL04AA28 — Belatacept
AHFS Codes
  • 92:44
PDB EntriesNot Available
FDA labelDownload (582 KB)
MSDSDownload (479 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentDelayed Graft Function1
1Active Not RecruitingTreatmentImpaired Renal Function / Kidney Failure,Chronic1
1CompletedSupportive CareTransplantations1
1, 2CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
1, 2CompletedTreatmentRheumatoid Arthritis1
2Active Not RecruitingTreatmentAcute Antibody Mediated Rejection / Mild Immunologic Risk Factor / Transplant, Kidney1
2Active Not RecruitingTreatmentProteinuria1
2Active Not RecruitingTreatmentTransplantation, Kidney1
2Active Not RecruitingTreatmentTransplantation, Organ1
2CompletedPreventionRejection, Transplant / Transplantation, Kidney / Transplantation, Renal1
2CompletedTreatmentDiabetes, Diabetes Mellitus Type 12
2CompletedTreatmentDisorder Related to Renal Transplantation1
2CompletedTreatmentTransplant, Kidney2
2CompletedTreatmentTransplantation, Renal1
2RecruitingTreatmentDelayed Graft Function / Transplant, Kidney1
2RecruitingTreatmentImmunosuppression1
2TerminatedTreatmentPrimary Renal Allograft Candidate / Transplantation, Kidney1
2TerminatedTreatmentPrimary Simultaneous Kidney and Pancreas Allograft Candidates / Simultaneous Kidney and Pancreas Transplantation1
2TerminatedTreatmentTransplant, Kidney1
2TerminatedTreatmentTransplantation, Kidney / Transplantation, Renal1
3Active Not RecruitingTreatmentTransplantation, Kidney1
3RecruitingTreatmentFailing Renal Allograft / Transplant, Kidney1
4Active Not RecruitingPreventionKidney Transplant Rejection1
4Active Not RecruitingTreatmentTransplantation, Renal1
4CompletedBasic ScienceRejection, Transplant1
4CompletedTreatmentRenal Toxicity1
4CompletedTreatmentTransplantation, Kidney1
4Not Yet RecruitingTreatmentTransplantations1
4RecruitingSupportive CareTransplantation, Kidney1
4RecruitingTreatmentAntibody Mediated Rejection / End Stage Renal Disease (ESRD)1
4RecruitingTreatmentEBV / Transplant; Failure, Kidney1
4RecruitingTreatmentImplant or Graft; Rejection1
4Unknown StatusNot AvailableNew Onset Diabetes After Transplant / Transplantation, Kidney1
Not AvailableActive Not RecruitingNot AvailableTransplantation, Kidney1
Not AvailableApproved for MarketingNot AvailableTransplantation, Renal1
Not AvailableCompletedNot AvailableRheumatoid Arthritis1
Not AvailableRecruitingTreatmentEnd-Stage Renal Disease (ESRD)1
Not AvailableWithdrawnTreatmentDiabetes, Diabetes Mellitus Type 1 / Islets of Langerhans Transplantation / Transplantation, Kidney1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous250 mg
Injection, powder, lyophilized, for solutionIntravenous250 mg/1
PricesNot Available
PatentsNot Available
Properties
StateLiquid
Experimental PropertiesNot 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
unknown
General Function:
Virus receptor activity
Specific Function:
Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4. May play a critical role in the early events of T-cell activation and costimulation of naive T-cells, such as deciding between immunity and anergy that is made by T-cells within 24 hours after activation. Isoform 2 interferes with the formation of CD86 ...
Gene Name:
CD86
Uniprot ID:
P42081
Uniprot Name:
T-lymphocyte activation antigen CD86
Molecular Weight:
37681.97 Da
References
  1. Vincenti F: Costimulation blockade in autoimmunity and transplantation. J Allergy Clin Immunol. 2008 Feb;121(2):299-306; quiz 307-8. doi: 10.1016/j.jaci.2008.01.002. [PubMed:18269922 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Virus receptor activity
Specific Function:
Involved in the costimulatory signal essential for T-lymphocyte activation. T-cell proliferation and cytokine production is induced by the binding of CD28, binding to CTLA-4 has opposite effects and inhibits T-cell activation.(Microbial infection) Acts as a receptor for adenovirus subgroup B.
Gene Name:
CD80
Uniprot ID:
P33681
Uniprot Name:
T-lymphocyte activation antigen CD80
Molecular Weight:
33047.625 Da
References
  1. Yabu JM, Vincenti F: Novel immunosuppression: small molecules and biologics. Semin Nephrol. 2007 Jul;27(4):479-86. [PubMed:17616278 ]
  2. Tedesco Silva H Jr, Pinheiro Machado P, Rosso Felipe C, Medina Pestana JO: Immunotherapy for De Novo renal transplantation: what's in the pipeline? Drugs. 2006;66(13):1665-84. [PubMed:16978033 ]
Drug created on March 19, 2008 10:48 / Updated on June 08, 2017 13:23