Cyclosporin B, EvoPure is a dihydroxylated metabolite of cyclosporin A (CsA). Cyclosporin B (M-26) and other cyclosporin metabolites have been found to have lower (<10%) immunosuppressant activity than cyclosporin A (CsA). Cyclosporin B and other metabolites have been isolated and characterized but do not appear to have been extensively studied.
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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) immunosuppressant 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).|
|References||Anderson MA and Gusella JF (1984) Use of Cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro 20(11):856-858. PMID 6519667 |
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