1. Product Overview
Cyclosporin A (CAS 2003234-63-5), also known as Cyclosporine or CsA, is a neutral, hydrophobic, cyclic undecapeptide (11 amino acids) of fungal origin (Tolypocladium inflatum, formerly Trichoderma polysporum). With the molecular formula C₆₂H₁₁₁N₁₁O₁₂ and a molecular weight of 1,202.61 g/mol, it is the most abundant and biologically active component of the Cyclosporin complex (A–H). Cyclosporin A binds to cyclophilin (immunophilin) to form a complex that inhibits calcineurin, thereby preventing nuclear translocation of NFAT (Nuclear Factor of Activated T-cells) and blocking IL-2 production. This results in potent immunosuppression selective for T-lymphocytes. It is the gold-standard reference for immunosuppressive therapy research, organ transplantation studies, and autoimmune disease modeling.
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2. Key Features and Benefits
• Potent & Selective Immunosuppression: Inhibits T-cell activation with IC₅₀ ~10–100 nM in vitro (IL-2 production) while sparing B-cells and other immune compartments at therapeutic concentrations.
• Well-Defined Mechanism: Binds cyclophilin A (Kd ~1–10 nM) → inhibits calcineurin phosphatase activity → blocks NFAT dephosphorylation and nuclear translocation → suppresses IL-2, IL-4, IFN-γ transcription.
• Proven Clinical Relevance: The foundational immunosuppressant for solid organ transplantation (kidney, liver, heart, lung) with >30 years of clinical use; >15,000 peer-reviewed publications validate its pharmacological profile.
• Multi-Pathway Research Tool: Beyond immunosuppression, CyA is used to study mitochondrial permeability transition pore (mPTP) regulation, cancer cell apoptosis, and neurodegenerative disease mechanisms.
• High Purity & Batch Consistency: Supplied at ≥95% or ≥98% (HPLC), with full CoA including peptide mapping, amino acid analysis, and residual solvent testing.
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3. Major Applications
• Immunosuppression & Transplantation Research: The primary reference standard for in vitro and in vivo immunosuppressive studies—mixed lymphocyte reactions (MLR), cytotoxic T-lymphocyte (CTL) assays, and graft-versus-host disease (GVHD) models.
• Autoimmune Disease Modeling: Employed in animal models of rheumatoid arthritis, multiple sclerosis (EAE), type 1 diabetes, and inflammatory bowel disease to evaluate immunosuppressive efficacy.
• NFAT & Calcineurin Signaling: Used to dissect the calcineurin-NFAT pathway in T-cell receptor (TCR) signaling, cytokine gene transcription, and lymphocyte development.
• Mitochondrial Research (mPTP): At high concentrations (1–10 μM), CyA binds to cyclophilin D (CypD) in the mitochondrial matrix, inhibiting mPTP opening and protecting against mitochondrial membrane potential collapse and apoptosis.
• Cancer & Apoptosis Studies: Investigated for its ability to modulate tumor cell survival, angiogenesis, and metastasis through calcineurin-dependent and -independent pathways.
• Neuroprotection Research: Applied in models of cerebral ischemia, Alzheimer's, and Parkinson's disease, where mPTP inhibition and calcineurin modulation confer neuroprotective effects.
• Drug-Drug Interaction & Pharmacokinetics: Used in CYP3A4/PGP inhibition studies (Cyclosporin is a known substrate and inhibitor), drug metabolism screening, and bioavailability assessment.
• Analytical Reference Standard: Serves as a standard for HPLC, LC-MS/MS quantification of Cyclosporin A in biological matrices (whole blood, plasma, tissue) in clinical therapeutic drug monitoring (TDM).
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4. Technical Specifications
Item Description
Product Name Cyclosporin A (CyA / CsA)
Synonyms Cyclosporine A; Cyclosporin A; [R-(E)]-cyclic(D-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-3-hydroxy-N,4-dimethyl-L-2-amino-6-octenoyl-L-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl)
CAS Number 2003234-63-5
Molecular Formula C₆₂H₁₁₁N₁₁O₁₂
Molecular Weight 1,202.61 g/mol
MDL Number —
PubChem CID 5284371
Assay (Purity) ≥95% / ≥98% (HPLC)
Appearance White to off-white crystalline powder
Melting Point 148–151 °C (Literature)
Boiling Point Not applicable (decomposes before boiling)
Density ~1.13 g/cm³ (Predicted)
pKa (Predicted) ~10.5–12.0 (N-terminal NH); ~3.5–4.5 (side chain COOH)
Calculated LogP ~6.5–8.0 (highly lipophilic cyclic peptide)
Polar Surface Area (PSA) ~269 Ų
Hydrogen Bond Donors 7–9 (peptide NH + OH)
Hydrogen Bond Acceptors 12 (C=O ×11, OH)
Rotatable Bonds 30–35
Solubility Soluble: Ethanol (~20–50 mg/mL), Methanol (~10–30 mg/mL), DMSO (~10–40 mg/mL, sonication recommended), DMF, Acetone, Ethyl acetate, DCM, Chloroform, THF.
Practically Insoluble:Water (<0.01 mg/mL at pH 7); formulations use surfactants (Cremophor EL, polysorbate 80) or cyclodextrins for solubilization.
Note:High lipophilicity; may require co-solvents or surfactants for biological assays.
Spectral Data (Literature) ¹H NMR (CDCl₃, 400 MHz): Complex multiplets from 0.70–4.50 ppm (aliphatic/amino acid CH/CH₂/CH₃), olefinic CH ~5.25 ppm, amide NH ~7.0–8.5 ppm.
¹³C NMR (CDCl₃):δ 10–60 (aliphatic), 110–175 (olefinic + amide C=O).
UV-Vis (MeOH):λmax ~205–210 nm (peptide bond), no visible absorbance.
SMILES Complex 62-carbon cyclic peptide — see structural formula in CoA
InChI Key HBYLMAVCSAYDQE-UHFFFAOYSA-N
Storage (Powder) -20°C, sealed, protected from light & moisture; stable ≥3–5 years
Solution Stability DMSO/ethanol stocks stable at -20°C for 6–12 months; avoid repeated freeze-thaw; working dilutions should be used within 24 h (slow precipitation may occur in aqueous buffers)
HS Code 2941.90.90 / 3822.90.00 (Research Tool)
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5. Storage and Handling
• Powder Storage: Store sealed vial at -20°C (or -80°C for long-term), protected from light in a desiccated environment. Cyclosporin A is a stable cyclic peptide with excellent long-term stability—≥3–5 years from date of manufacture under proper conditions.
• Stock Solution: Dissolve in anhydrous ethanol (20–50 mg/mL) or DMSO (10–40 mg/mL). Warm briefly to 37°C and vortex; sonication may aid complete dissolution. The compound is highly lipophilic—aqueous solutions will precipitate.
• Working Dilution: For cell culture assays, dilute into medium containing 0.1–1% DMSO + surfactant (e.g., 0.05% Cremophor EL or 0.1% polysorbate 80) to maintain solubility. Final DMSO ≤0.1%. For in vivo studies, prepare in 5% DMSO + 95% corn oil, or 10% ethanol + 20% Cremophor EL + 70% saline.
• Formulation Note: Cyclosporin A's water insolubility is a well-known formulation challenge; clinical formulations use Cremophor EL (polyethoxylated castor oil) or lipid-based delivery systems. Research labs should follow similar principles.
• Freeze-Thaw: Aliquot DMSO/ethanol stocks upon preparation. Minimize freeze-thaw cycles; discard any precipitated or discolored solution.
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6. Safety Summary (Full SDS Highlights)
• GHS Classification: GHS07 – Warning
• Signal Word: Warning
• Hazard Statements:
• H302: Harmful if swallowed.
• H312: Harmful in contact with skin.
• H315: Causes skin irritation.
• H319: Causes serious eye irritation.
• H335: May cause respiratory irritation.
• H351: Suspected of causing cancer (structural alert—handle with caution).
• H361: Suspected of damaging fertility or the unborn child (Reproductive Category 2).
• Precautionary Statements:
• P201: Obtain special instructions before use.
• P260: Do not breathe dust/mist/vapors. Use only in a well-ventilated area or fume hood.
• P261: Avoid breathing dust/mist/vapors.
• P264: Wash hands, forearms, and face thoroughly after handling.
• P270: Do not eat, drink, or smoke in areas where this material is used.
• P271: Use only outdoors or in a well-ventilated area.
• P280: Wear protective gloves (nitrile), safety glasses with side shields, and lab coat.
• P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or physician.
• P302+P352: IF ON SKIN: Wash with plenty of soap and water.
• P304+P340: IF INHALED: Remove person to fresh air and keep comfortable for breathing.
• P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do. Continue rinsing.
• P308+P311: IF exposed: Call a POISON CENTER or physician.
• P330: Rinse mouth if swallowed.
• P405: Store locked up.
• P501: Dispose of contents/container in accordance with local, regional, and national regulations.
• First Aid Measures:
• Inhalation: Remove to fresh air immediately. If breathing difficult, administer oxygen and seek medical attention.
• Skin Contact: Immediately wash with plenty of soap and water for at least 15 minutes. Remove contaminated clothing. Seek medical advice if irritation or rash develops.
• Eye Contact: Flush immediately with copious lukewarm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention immediately.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Call a POISON CENTER immediately.
• Fire-Fighting Measures:
• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.
• Special Hazards: Combustion may produce irritating/acrid smoke (CO, NOₓ). Nitrogen oxides are toxic.
• Protective Equipment: Wear self-contained breathing apparatus (SCBA) and full protective clothing.
• Spill Response:
• Avoid dust generation. Sweep up and place in a suitable closed container for disposal. Do not allow entry to drains or waterways. Ventilate area after cleanup.
• Handling & Storage:
• Handle in fume hood ONLY. Keep container closed when not in use. Store at -20°C, protected from light and moisture. Keep away from strong oxidizers and heat sources.
• Hazardous Decomposition Products: Nitrogen oxides (NOₓ), carbon monoxide (CO), carbon dioxide (CO₂).
• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a potent immunosuppressive and potentially teratogenic compound.
