M.W. 1202.61

C62H111N11O12

[59865-13-3]

M.I. 12:  2821

M.I. 14:  2752

Storage:  Store at or below -20 ?C.  Solubility:  Soluble in DMSO at 100 mg/mL; soluble in ethanol at 200 mg/mL; very poorly soluble in water; maximum solubility in plain water is estimated to be about 5-10 ?M; buffers, serum, or other additives may increase or decrease the aqueous solubility.  Disposal:  A

Cyclic hydrophobic oligopeptide isolated from the filamentous fungi, Tolypocladium inflatum, with potent immunosuppressant properties.  Induces apoptosis in rat thymocytes and in murine B cell lymphoma cells, but prevents apoptosis in BLB cell lines induced by anti-IgM and ionomycin.  Donjerkovic, D., et al.  "Regulation of p27Kip1 accumulation in murine B-lymphoma cells: role of c-Myc and calcium."  Cell. Growth Differ. 10:  695-704 (1999).  Mordvinov, V.A., et al.  "A human T-cell line with inducible production of interleukins 5 and 4.  A model for studies of gene expression."  J. Immunol. Methods 228:  163-168 (1999).  Zaidan, E., et al.  "Cyclosporin A-sensitive changes in mitochondrial glutathione are an early response to intrastiatal NMDA or forebrain ischemia in rats."  J. Neurochem. 73:  2214-2217 (1999).  Gottschalk, A.R., et al.  "Identification of immunosuppressant-induced apoptosis in a murine B-cell line and its prevention by bcl-x but not bcl-2."  Proc. Natl. Acad. Sci. USA 91:  7350-7354 (1994).

The complex of cyclosporin A with the protein cyclophilin inhibits T-cell receptor signal transduction pathway via the inhibition of calcineurin (protein phosphatase 2B) with nanomolar affinity (Ki = 270 nM).  Etzkorn, F.A., Chang, Z.Y., Stolz, L.A., Walsh, C.T.  "Cyclophilin residues that affect noncompetitive inhibition of the protein serine phosphatase activity of calcineurin by the cyclophilin-cyclosporin A complex."  Biochemistry 33:  2380-2388 (1994).  Liu, J.  "FK506 and ciclosporin: molecular probes for studying intracellular signal transduction."  Trends Pharmacol. Sci. 14:  182-188 (1993).

Inhibits interleukin-1α-, lipopolysaccharide-, and TNF-α-nitric oxide synthesis induction.  Fast, D.J., et al.  "Cyclosporin A inhibits nitric oxide production by L929 cells in response to tumor necrosis factor and interferon-gamma."  J. Interferon Res. 13:  235-240 (1993).  Marumo, T., et al.  "Cyclosporin A inhibits nitric oxide synthase induction in vascular smooth muscle cells."  Hypertension 25:  764-768 (1995).  Hattori, Y., and Naranishi, N.  "Effects of cyclosporin A and FK506 on nitric oxide and tetrahydrobiopterin synthesis in bacterial lipopolysaccharide-treated J774 macrophages."  Cell Immunol. 165:  7-11 (1995).

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