Cyclosporine, USP (syn: Cyclosporin,Cyclosporin A) is a natural product and cyclic polypeptide derived from fungi. It is a macrolide with potent immunosuppressive properties. Cyclosporine was isolated in 1971 from the soil fungus Tolypocladium inflatum (Sandoz, now Novartis), and the Norwegian strain is currently used for mass production of this compound. Its immunosuppressive properties were discovered in 1971 via a screening test (Sandoz). Cyclosporine metabolites include Cyclosporin B, D, E, H, and L. Cyclosporine, USP is soluble in DMSO and ethanol. It has very poor water solubility.
|Mechanism of Action||After entering a T-cell, Cyclosporine associates with the cytosolic protein cyclophilin which helps in protein folding. Cyclosporine binds to cyclophilins and this complex binds another cytosolic protein phosphatase called Calcineurin (protein phosphatase 2B) that dephosphorylates a transcription factor (nuclear factor of activated T-cells, or NF-AT) needed for expression of interleukin 2 (IL-2.). It also blocks the pathway to nitric oxide synthesis via tumor necrosis factor (TNFa) and Interleukin 1a.|
|General Applications||D-Cyclosporine has been used as an internal standard for the quantification of cyclosporin A.|
|Cancer Applications||The Immunosuppressive properties and potential toxicity of Cyclosporine can be studied during in vitro assays. Other metabolites of Cyclosporine A (AM1, AM1c, DihydroAM1, AM19, and AM4N) can also be studied (Vollenbroeker B et al, 2005).|
Matsuda S and Koyasu S (2000) Mechanisms of action of Cyclosporine. Immunopharmacol. 47(2-3): 119-125. PMID 10878286
Matsuda, S (2000) Mechanisms of action of Cyclosporine. Immunopharmacol. 47(2-3):119-125. PMID 10878286
Vollenbroeker B et al (2005) Determination of cyclosporine and its metabolites in blood via HPLC-MS and correlation to clinically important parameters. Transplant Proc. 37(4):1741-1744 PMID 15919451