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| 1mg |
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| Targets |
The primary targets of Abatacept are the CD80 and CD86 molecules (also known as B7-1 and B7-2) found on the surface of antigen-presenting cells (APCs). As a CTLA-4-Ig fusion protein, Abatacept binds to these CD80/CD86 ligands with high affinity. This binding competitively blocks their interaction with CD28 on T lymphocytes. The CD28-CD80/CD86 interaction is a critical co-stimulatory signal required for full T-cell activation. By blocking this signal, Abatacept effectively inhibits T-cell activation and downstream immune responses.
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| ln Vitro |
In vitro, Abatacept (100 ug/mL) blocks the CD80/86:CD28 costimulatory axis, thereby inhibiting T-cell proliferation in co-culture assays of primary CD4+ T cells and APCs. In ex vivo analysis of cells from patients with LRBA deficiency, Abatacept modulates CTLA-4 expression levels and restores regulatory T cell function. These studies demonstrate that Abatacept can directly inhibit T-cell activation and has the potential to correct immune dysregulation, supporting its use as an immunosuppressive and immunomodulatory agent.
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| ln Vivo |
In comparison to the intravenous group, abatacept significantly reduced leg edema in the subcutaneous multiple-dose group (tobs=2.50)[2]. Across the whole dose range under investigation, abatacept showed linear PK. The bottle volume (Vss) is 146 mL/kg, the NCA clearance (CL) is 20.8 mL/day/kg, and the subcutaneous spray's bioavailability (F) is 57.7% [2]. Oral abatacept (10 mg/kg; every 2 days) decreases the percentage of T cells that are activated (CD44highCD62L–) and prevents the elevation of CD71 and ICOS in homozygous DO11.10 RAG-2–/– BALB/c (H-2d /d) s[3].
In vivo, Abatacept has demonstrated efficacy in rodent models of autoimmune disease. In a rat model of collagen-induced arthritis, subcutaneous administration of Abatacept (0.1, 1, 10 mg/kg) led to a dose-dependent reduction in paw edema. In mouse T-cell priming models, systemic administration of Abatacept (0.5 mg/mouse) inhibited antigen-specific T-cell activation and expansion. These preclinical findings support its clinical use in treating rheumatoid arthritis by specifically and effectively modulating the T-cell costimulatory pathway to reduce inflammation and joint damage. |
| Enzyme Assay |
Cell-free receptor binding assays for Abatacept typically involve surface plasmon resonance (SPR) or enzyme-linked immunosorbent assays (ELISA) to study its interaction with CD80 and CD86. A standard protocol involves immobilizing recombinant human CD80 or CD86 on a sensor chip (for SPR) or on a microtiter plate (for ELISA). The Abatacept fusion protein is then flowed over the immobilized ligand at various concentrations. The binding affinity (Kd) is determined from the association and dissociation rates. ELISA-based assays use a labeled secondary antibody to detect bound Abatacept, providing a quantitative measure of its binding to the target.
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| Cell Assay |
For in vitro cellular experiments, primary human CD4+ T cells and antigen-presenting cells (APCs) are co-cultured in the presence of a specific antigen or a stimulatory antibody. Abatacept is added at various concentrations (e.g., 0.1-100 ug/mL). After several days of culture, T-cell proliferation is measured by [3H]-thymidine incorporation or flow cytometry-based CFSE dilution assays. Cytokine production (e.g., IL-2, IFN-gamma) in the supernatant is measured by ELISA. The degree of inhibition of T-cell activation and proliferation is used to assess the in vitro potency of Abatacept.
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| Animal Protocol |
Animal/Disease Models: Male Lewis rats (6-9 weeks old) weighing 150-175 g[2]
Doses: 10 mg/kg daily (IV), 20 mg/kg (SC single dose), 20 mg/kg ( SC multiple doses) 21 subcutaneous injection of 10 mg/kg on days 23, 25, 27 and 29 Dosage Route of Administration: intravenous (iv) (iv)or subcutaneous injection Experimental Results: paw edema was diminished, and the paw edema in the subcutaneousmultiple dose group was compared with the control group Edema reduction was Dramatically greater (tobs = 2.50) in the IV dose group. Animal/Disease Models: Male Lewis rat (6-9 weeks old), body weight 150-175 g[2] Doses: 10 mg/kg (IV), 20 mg/kg (SC single dose), 20 mg/kg (SC) Multiple doses) 10 mg/kg subcutaneously (sc) (sc) on Day 21, Days 23, 25, 27 and 29 (pharmacokinetic/PK/PK study) Dosing: IV or SC Experimental Results: NCA clearance (CL) was 20.8 mL/ day/kg, the volume (Vss) is 146mL/kg, and the bioavailability (F) of SC dose administration is 57.7%. In vivo animal experiments with Abatacept are typically conducted in rodent models of autoimmune disease. A common protocol involves administering Abatacept subcutaneously or intravenously to rats or mice. In the collagen-induced arthritis model, male Lewis rats are given doses of 0.1, 1, and 10 mg/kg. Dosing schedules can be single-dose or multiple-dose, for example, 20 mg/kg on day 21 followed by 10 mg/kg on days 23, 25, 27, and 29. Disease progression is monitored by measuring paw edema, clinical arthritis scores, and joint histopathology to assess the compound's efficacy. |
| ADME/Pharmacokinetics |
Abatacept is a large recombinant fusion protein with a molecular weight of approximately 92 kDa. As a protein therapeutic, it is administered via subcutaneous (SC) or intravenous (IV) injection. It is supplied as a sterile solution in a buffered formulation. Its pharmacokinetic profile is characterized by a slow clearance and a long half-life (approximately 13 days in humans), which allows for intermittent dosing. It is stored at low temperature (2-8degC) and should not be frozen. Its bioavailability is high following SC administration.
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| Toxicity/Toxicokinetics |
The toxicity profile of Abatacept is generally favorable, reflecting its targeted mechanism of action. Common adverse effects include headache, upper respiratory tract infections, and nasopharyngitis. Because it inhibits T-cell activation, there is a potential for increased risk of infections and malignancies, which is a class effect of immunomodulatory therapies. Serious adverse events are rare but can include infusion-related reactions and hypersensitivity. It is contraindicated in patients with severe, uncontrolled infections. For research use only; not for human therapeutic use.
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| References |
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| Additional Infomation |
Abatacept (Orencia) is a first-in-class, selective T-cell costimulation modulator. It is a recombinant fusion protein composed of the extracellular domain of human CTLA-4 linked to a modified Fc portion of human IgG1. It binds to CD80 and CD86 on APCs, blocking the CD28-mediated costimulatory signal required for T-cell activation. This immunosuppressive activity makes it an effective treatment for rheumatoid arthritis and juvenile idiopathic arthritis, and it is also studied for other autoimmune conditions.
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| CAS # |
332348-12-6
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| Appearance |
Colorless to light yellow liquid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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