Overview
Cyclosporin A (CsA) is a cyclic undecapeptide derived from the fungus Tolypocladium inflatum. It was first isolated in 1970 and revolutionized organ transplantation by suppressing T-cell activation. Its unique mechanism of action involves binding to cyclophilin, inhibiting calcineurin, and blocking interleukin-2 production. CsA is a cornerstone in immunosuppressive therapy, particularly for kidney, liver, and heart transplants. Beyond clinical use, it serves as a research tool in immunology and cell biology due to its specific inhibition of calcineurin-dependent pathways.
Physical and Chemical Properties
Cyclosporin A is a white crystalline powder with a molecular weight of 1202.61 g/mol. It melts at 148-151°C and is highly lipophilic, explaining its poor water solubility but excellent solubility in organic solvents like ethanol and DMSO. The peptide structure includes unusual amino acids like MeBmt (N-methyl-4-but-2-enyl-4-hydroxy-L-threonine), contributing to its stability and bioactivity. Its hydrophobic nature necessitates formulation with emulsifiers (e.g., Sandimmune®) for oral or intravenous delivery in clinical settings.
Main Applications
The primary use of Cyclosporin A is in preventing organ transplant rejection by selectively inhibiting T-cell proliferation. It is also prescribed for severe autoimmune disorders, including psoriasis, atopic dermatitis, and rheumatoid arthritis, where conventional therapies fail. In research, CsA is employed to study T-cell signaling pathways, mitochondrial permeability transition, and neurodegenerative diseases. Off-label applications include dry eye syndrome (Restasis®) and veterinary medicine for immune-mediated conditions in pets.
Safety and Storage
Cyclosporin A requires careful handling due to its toxicity. Use nitrile gloves and fume hoods to avoid exposure. Chronic use can lead to kidney damage, hypertension, and increased infection risk, necessitating therapeutic drug monitoring. Store CsA at 2-8°C in airtight, light-resistant containers. Avoid temperature fluctuations and humidity to prevent degradation. Solutions in DMSO should be aliquoted and frozen at -20°C for long-term stability.
B2B Procurement Guide
When procuring Cyclosporin A, prioritize suppliers compliant with Good Manufacturing Practice (GMP) for pharmaceutical-grade material. Key specifications include HPLC purity (≥98%), endotoxin levels (<0.1 EU/mg), and residual solvent analysis. Bulk buyers should request certificates of analysis (CoA), stability data, and supply chain transparency. Prices vary by quantity and purity; negotiate contracts with accredited distributors like Novartis or Teva for consistent quality.