Cyclosporin B, EvoPure® is the dihydroxylated metabolite of Cyclosporin A. Cyclosporin B (M-26) and other Cyclosporin metabolites have been found to have lower (<10%) immunosuppressive activity compared Cyclosporin A. Cyclosporin B and other metabolites have been isolated and characterized but have not been extensively studied.
EvoPure® products have been fully characterized by spectral analysis and are shipped with a comprehensive certificate of analysis containing lot-specific HPLC, MS, HNMR, and FTIR data.
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|Mechanism of Action||Cyclosporin B (and other Cyclosporin A metabolites) have lower immunosuppressive activity but likely operate under the same mechanism as Cyclosporin A described below.
After entering a T-cell, Cyclosporin A associates with the cytosolic protein cyclophilin which helps in protein folding. Cyclosporin A 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. Cyclosporin A (CsA) immunosuppressive activity stems from its ability to prevent T-cell activation by blocking specific cytokine transcription genes. After entering a T-cell, cyclosporin A (CsA) associates with ubiquitous cytosolic proteins called cyclophilins which aid in protein folding. Cyclosporin A (CsA) : cyclophilin complexes together bind calcineurin, (another cytosolic protein) effectively blocking the pathway to IL-2 gene transcription and T-cell activation.
|Eukaryotic Cell Culture Applications||Cyclosporins have used as tools to study complex biological networks and pathways, involving protein function, and protein-protein interactions.|
|Cancer Applications||Cyclosporin’s immunosuppressive properties and potential toxicity can be studied during in vitro assays. Other metabolites of Cyclosporin A (AM1, AM1c, DihydroAM1, AM19, and AM4N) can also be studied (Vollenbroeker B et al, 2005).|
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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
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Watashi K, Hijikata M, Hosaka M, Yamaji M and Shimotohno K (2003) Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatol. 38(5):1282-1288. PMID 14578868
Zheng XS, Chan T, and Zhou HH (2004) Genetic and genomic approaches to identify and study the targets of bioactive small molecules. Chem and Biol 11(5):609-618 PMID 15157872