Cyclosporin A ReadyMade™ Solution

- Overview
  - Cyclosporin A ReadyMade™ Solution is a sterile-filtered (0.2 μm) solution of Cyclosporin A that has been dissolved in DMSO at a concentration of 5 mg/ml, ready for use in a variety of applications. Cyclosporin A is a natural product, a non-polar cyclic oligopeptide and calcineurin inhibitor with immunosuppressive properties. It was first isolated in 1971 from the fungus Tolypocladium inflatum. It can be used in organ-on-a-chip models to study nephrotoxicity and is also being studied for utility for coronavirus (SARS-CoV-2).
    
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    Background
    
    Cyclosporin A can inhibit function of many nuclear proteins involved in T-cell activation at the level of mRNA transcription. It forms a complex with cyclophilin, which can bind to calcineurin, a Ca2+- and calmodulin-dependent protein phosphatase, inhibiting its enzymatic activity.
- Properties
  - CAS Number
    
    59865-13-3
    
    Molecular Formula
    
    C62H111N11O12
    
    Molecular Weight
    
    1202.61
    
    Other Properties
    
    Source: Tolypocladium inflatum
    
    Storage
    
    -20°C
    
    * For research use only
- Applications
  - Application Description
    
    Microbiology Applications: Cyclosporin A was found to suppress hepatitis C replication in cultured hepatocytes. Cyclosporine has been shown to inhibit SARS-CoV replication at very low doses. Similarly, it inhibits the replication of other coronaviruses and HIV. There is a resemblance between SARS-CoV-2 and SARS-CoV based on the full-length genome. Further research is needed to understand its utility for SARS-CoV-2 (Cure et al, 2020).
    Disruption of the csr-1 gene, which encodes the cyclosporin A-binding protein, leads to the resistance to Cyclosporin A. By cloning a gene of interest into a csr-1 knock-in vector and transforming a fungus with it, one can easily insert any gene, in single-copy, into a defined locus (Bardiya N. et al (2007)
    
    Eukaryotic Cell Culture Applications: Cyclosporin A has been used to test its toxic effect on a 3D proximal tubule model on a perfusable organ-on-a chip model. Bioprinting is used to create 3D human renal proximal tubules in vitro. When Cyclosporin is introduced, this nephrotoxin causes disruption of the epithelial barrier in a dose-dependent manner. This system is useful for drug screening, disease modeling, and kidney organ engineering (Homan et al, 2016).
    Cyclosporins have used as tools to study complex biological networks and pathways, involving protein function, and protein-protein interactions. Cyclosporin A had a suppressive effect on the Hepatitis C virus (HCV) replicon at the RNA level and HCV protein expression in cultured hepatocytes. Cyclosporin A also inhibited multiplication of the HCV genome in a human hepatocyte cell line infected with HCV using HCV-positive plasma (Watashi et al, 2003). Cyclosporin A has been used to establish Epstein-Barr virus-transformed human lymphoblastoid cell lines (Anderson and Gusella 1984).
    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).