Belatacept
Identification
- Summary
Belatacept is a selective T-cell costimulation blocker used in the prophylaxis of organ rejection in adult patients receiving a kidney transplant.
- Brand Names
- Nulojix
- Generic Name
- Belatacept
- DrugBank Accession Number
- DB06681
- Background
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. Belatacept is only 2 amino acids different from abatacept (Orencia). FDA approved on June 15, 2011.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Fusion proteins - Protein Chemical Formula
- C3508H5440N922O1096S32
- Protein Average Weight
- 92300.0 Da (with glycosylation)
- Sequences
> sequence for belatacept MHVAQPAVVLASSRGIASFVCEYASPGKYTEVRVTVLRQADSQVTEVCAATYMMGNELTF LDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYEGIGNGTQIYVIDPEPC PDSDQEPKSSDKTHTSPPSPAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format- Synonyms
- Belatacept
- External IDs
- BMS-224818
- BMS224818
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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in prevention of Kidney transplant rejection •••••••••••• ••••• •••••••••••• ••••• •••••••••••• - Contraindications & Blackbox Warnings
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- 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.
Target Actions Organism AT-lymphocyte activation antigen CD86 antagonistHumans AT-lymphocyte activation antigen CD80 antagonistHumans - 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 binding
Not 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 elimination
Not 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.
- Adverse Effects
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- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Belatacept. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Belatacept. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Belatacept. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Belatacept. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Belatacept. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Nulojix Injection, powder, for solution 250 mg Intravenous Bristol Myers Squibb Pharma Eeig 2016-09-08 Not applicable EU Nulojix Injection, powder, lyophilized, for solution 250 mg/1 Intravenous E.R. Squibb & Sons, L.L.C. 2011-06-15 Not applicable US Nulojix Injection, powder, for solution 250 mg Intravenous Bristol Myers Squibb Pharma Eeig 2016-09-08 Not applicable EU
Categories
- ATC Codes
- L04AA28 — Belatacept
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antineoplastic Agents, Immunological
- Antineoplastic and Immunomodulating Agents
- Antirheumatic Agents
- Blood Proteins
- CD80-directed Antibody Interactions
- CD86-directed Antibody Interactions
- Globulins
- Immune Checkpoint Inhibitors
- Immunoconjugates
- Immunologic Factors
- Immunosuppressive Agents
- Proteins
- Selective Immunosuppressants
- Selective T Cell Costimulation Blocker
- Serum Globulins
- T Lymphocyte Costimulation Activity Blockade
- Chemical TaxonomyProvided by Classyfire
- 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
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- E3B2GI648A
- CAS number
- 706808-37-9
References
- General References
- 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. [Article]
- Garnock-Jones KP: Belatacept: in adult kidney transplant recipients. BioDrugs. 2012 Dec 1;26(6):413-24. doi: 10.2165/11208900-000000000-00000. [Article]
- FDA Approved Drug Products: Nulojix (beltacept) for intravenous injection [Link]
- External Links
- KEGG Drug
- D03222
- PubChem Substance
- 347910359
- 1112973
- ChEMBL
- CHEMBL1742990
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Belatacept
- FDA label
- Download (582 KB)
- MSDS
- Download (479 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Basic Science Transplanted Organ Rejection 1 4 Completed Diagnostic Immunosuppression / Kidney Transplant Rejection 1 4 Completed Prevention Kidney Transplant Rejection 1 4 Completed Supportive Care Kidney Transplantation 1 4 Completed Treatment Epstein-Barr (EBV) / Kidney Failure, Kidney Transplant 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 250 MG Injection, powder, lyophilized, for solution Intravenous 250 mg/1 Injection, powder, lyophilized, for solution Intravenous 250 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- 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-cel...
- Gene Name
- CD86
- Uniprot ID
- P42081
- Uniprot Name
- T-lymphocyte activation antigen CD86
- Molecular Weight
- 37681.97 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- 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 an...
- Gene Name
- CD80
- Uniprot ID
- P33681
- Uniprot Name
- T-lymphocyte activation antigen CD80
- Molecular Weight
- 33047.625 Da
References
- Yabu JM, Vincenti F: Novel immunosuppression: small molecules and biologics. Semin Nephrol. 2007 Jul;27(4):479-86. [Article]
- 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. [Article]
Drug created at March 19, 2008 16:48 / Updated at April 30, 2021 13:06