Cyclosporin A, a cyclic 11-amino-acid peptide, acts as a second-generation immunosuppressant by blocking IL-2 production in T lymphocytes. This action reduces immune rejection and supports treatments like organ transplants and aplastic anemia. Its pharmacokinetics show oral bioavailability from 8%…
Cyclosporin A CsA consists of a cyclic chain of 11 amino acids. It includes a unique amino acid with 9 carbons and an ethylene double bond. As a second-generation immunosuppressant, CsA blocks T lymphocyte production through IL-2 regulation, which lessens the body's immune rejection response.
This makes CsA a reliable option for clinical use in immunosuppression. For detailed peptide structures, check the Peptide Glossary /tools/peptide-glossary .
CsA binds with cyclophilins CyP to form a complex. This complex then targets calcium/calmodulin-dependent calcineurin CaN , blocking nuclear factor of activated T cells NF-AT . Without dephosphorylation, NF-AT cannot enter the nucleus, halting IL-2 production and T lymphocyte growth.
CsA curbs IL-2 through two pathways. First, it directly suppresses IL-2 synthesis, the most sensitive effect, stopping cytotoxic T lymphocyte proliferation at concentrations of 10-20 ng. Second, it reduces IL-2 receptor expression, with inhibition around 100 ng·mL, further dampening cytotoxic T lymphocyte responses to IL-2.
CsA strengthens anti-rejection efforts in organ transplants. It treats graft-versus-host disease GVHD and sees the broadest use in kidney transplantation.
In aplastic anemia AA , CsA normalizes T lymphocyte activity and curbs negative regulators in blood production. For nephrotic syndrome, it enhances glomerular basement membrane pore size and charge selectivity, cutting proteinuria levels.
CsA also limits rheumatoid arthritis progression by suppressing synovial membrane factors like interleukin-21 IL-21 , interleukin-26 IL-26 , and tumor necrosis factor TNF . Researchers often use tools like the Dosage & Cycle Planner /tools/peptide-dosage-planner for such compounds.
CsA displays high lipophilicity, leading to variable oral bioavailability of 8% to 60%. Blood peak levels occur 1 to 8 hours post-dose.
It distributes widely, with a human volume of distribution at 2.9 to 7 L·kg⁻¹. CsA gathers in lymphoid tissues and fat-rich organs such as the liver and pancreas, while showing lower levels in the adrenals, fat, and brain.
Liver CYP3A4 handles most oxidative metabolism, with minor contributions from the intestinal wall and kidneys. Metabolites exit primarily via bile, with under 1% of unchanged CsA in urine or bile. Clearance stands at about 0.35 L·kg⁻¹·h⁻¹. The Half-Life Calculator /tools/peptide-half-life-plotter can help model these properties.
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CsA remains a cornerstone immunosuppressant due to its targeted IL-2 pathway blockade and proven roles in transplants and autoimmune conditions. Its pharmacokinetic traits demand careful dosing. Explore more at our Free peptide tools /tools .
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