Belimumab is an intravenous immunosupressant for the adjunctive treatment of systemic lupus erythematosus (SLE). More specifically, it is a fully human recombinant IgG1λ monoclonal antibody produced from a recombinant NS0 cell line stably transfected with the belimumab heavy chain and light chain genes. It is the first biological treatment approved for the indication of SLE. Concomitant use with live or inactivated vaccines must be avoided. Belimumab was FDA approved on March 9, 2011. Belimumab consists of 2 heavy chains, and 2 light chains of the lambda subclass. Each heavy chain contains 452 amino acid residues and each light chain contains 214 amino acid residues. There are 3 post-translational modifications: a conserved N-linked glycosylation on the CH2 domain at Asn 303 of the heavy chain, the conversion of the N-terminal glutamine residue of the heavy chain into pyroglutamate, and loss of C-terminal lysine residue of the heavy chain.
|Protein chemical formula||C6358H9904N1728O2010S44|
|Protein average weight||147000.0 Da|
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|Product Ingredients||Not Available|
|Approved Prescription Products|
|Approved Generic Prescription Products||Not Available|
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Adjunct treatment for auto-antibody-positive active systemic lupus erythematosus.
By the 52nd week of treatment with belimumab, a reduction in CD19+, CD20+, naive and activated B cells, plasma cells, plasmacytoid cells, and SLE B-cell subset can be observed. Reductions in plasma cells and SLE B-cell subset can be seen by the eighth week and these levels were maintained to week 52. Belimumab also reduced levels of IgG and anti-dsDNA.
|Mechanism of action|
Belimumab selectively binds to soluble human B lymphocyte stimulator protein (BLyS) so that BLyS is unable to bind to receptors on B lymphocytes. The binding of BLyS to its receptor is essential for the survival of B lymphocytes. Consequently, belimumab reduces B-cell mediated immunity and the autoimmune response.
Cmax, 10 mg/kg, SLE patients = 313 µg/mL; AUC (0-∞), 10 mg/kg, SLE patients = 3083.
|Volume of distribution|
Vdss, 10 mg/kg, SLE patients = 5.29 L.
|Protein binding||Not Available|
Because belimumab is a protein, it is expected that it is degraded into peptides and amino acids by proteolytic enzymes.
|Route of elimination||Not Available|
Terminal elimination half-life, 10 mg/kg, SLE patients= 19.4 days; Distribution half-life, 10 mg/kg, SLE patients = 1.75 days.
Systemic clearance, 10 mg/kg, SLE patients = 215 mL/day.
The most commonly-reported adverse reactions, occurring in ≥5% of patients in clinical trials were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis. The most common serious adverse reactions were serious infections.
|Pharmacogenomic Effects/ADRs||Not Available|
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|Synthesis Reference||Not Available|
|ATC Codes||L04AA26 — Belimumab|
|PDB Entries||Not Available|
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|Experimental Properties||Not Available|
|Super Class||Organic Acids|
|Class||Carboxylic Acids and Derivatives|
|Sub Class||Amino Acids, Peptides, and Analogues|
|Alternative Parents||Not Available|
|Molecular Framework||Not Available|
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- Pharmacological action
- General Function:
- Receptor binding
- Specific Function:
- Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.Isoform 2 seems to inhibit isoform...
- Gene Name:
- Uniprot ID:
- Molecular Weight:
- 31222.48 Da