DB01281 - Abatacept
| Identification | |||||||||||||
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| Name | Abatacept | ||||||||||||
| Accession Number | DB01281 | ||||||||||||
| Type | biotech | ||||||||||||
| Description | Abatacept 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). It is produced through recombinant DNA technology in mammalian cells. The drug has activity as a selective costimulation modulator with inhibitory activity on T lymphocytes. Although approved for the treatment of rheumatoid arthritis, Repligen has entered a slightly different formulation of CTLA4-Ig into clinical trials (RG2077). | ||||||||||||
| Structure |
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| Categories (*) | |||||||||||||
| Molecular Weight | 92 kDa | ||||||||||||
| Groups | approved | ||||||||||||
| Monoisotopic Weight | Not Available | ||||||||||||
| Pharmacology | |||||||||||||
| Indication | For the management of the signs and symptoms of moderate-to-severe active rheumatoid arthritis, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adult patients. It is indicated both as a monotherapy and for use in combination with a continued regimen of DMARDs (not including TNF antagonists). Also used for the management of the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children. | ||||||||||||
| Mechanism of action | Abatacept is a selective costimulation modulator, like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis. | ||||||||||||
| Absorption | When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%. | ||||||||||||
| Protein binding | Not Available | ||||||||||||
| Biotransformation | Not Available | ||||||||||||
| Route of elimination | Not Available | ||||||||||||
| Toxicity | Most common adverse events (>=10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect. | ||||||||||||
| Affected organisms |
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| Interactions | |||||||||||||
| Drug Interactions |
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| Food Interactions | Not Available | ||||||||||||
Targets
| T-lymphocyte activation antigen CD80 | |
|---|---|
| Name | T-lymphocyte activation antigen CD80 |
| Gene Name | CD80 |
| Pharmacological action | yes |
| Actions | antagonist |
| References |
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| DTHybrid score | 1.6162 |
| T-lymphocyte activation antigen CD86 | |
| Name | T-lymphocyte activation antigen CD86 |
| Gene Name | CD86 |
| Pharmacological action | yes |
| Actions | antagonist |
| References |
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| DTHybrid score | 1.5266 |
Predictions
| Id | Partner name | Gene Name | Score |
|---|---|---|---|
| 6063 | Major histocompatibility complex class I-related gene protein | MR1 | 0.0786 |
| 660 | T-cell surface glycoprotein CD1a | CD1A | 0.0786 |
| 5955 | T-cell surface glycoprotein CD4 | CD4 | 0.0786 |
| 6065 | Integrin beta-1 | ITGB1 | 0.0785 |
| 6066 | Integrin alpha-V | ITGAV | 0.0785 |
| 2039 | Integrin beta-3 | ITGB3 | 0.0595 |
| 572 | Integrin alpha-L | ITGAL | 0.0518 |
| 3820 | Low affinity immunoglobulin gamma Fc region receptor II-b | FCGR2B | 0.0432 |