Cyclosporine A 是一种能与亲环素结合的抑制剂。 根据它的作用机制可作为钙调神经磷酸酶抑制剂、细胞色素 P450 3A4 抑制剂和 P-糖蛋白抑制剂。

Cyclosporine A is a Calcineurin Inhibitor Immunosuppressant. The mechanism of action of cyclosporine is as a Calcineurin Inhibitor, and Cytochrome P450 3A4 Inhibitor, and P-Glycoprotein Inhibitor.

作为一种免疫抑制剂,Cyclosporin A临床上用于器官移植中预防免疫排斥.研究表明,在小鼠,大鼠,和荷兰猪中,Cyclosporin A经非肠道给药或者口服给药都有效.

Cyclosporin A对钙调磷酸酶具有抑制作用（IC50：7 nM）,并阻断NF-AT核转运。Cyclosporin A能够抑制MTP(线粒体通透性转换孔)的开放（IC50是39 nM）,从而影响线粒体。在T细胞中,Cyclosporin A与亲环蛋白(免疫亲和素)结合,形成亲环蛋白-Cyclosporin A复合体,其结合并抑制钙调磷酸酶。

Phosphatase Assay: Purified bovine brain calcineurin and calmodulin are purchased. Reaction mixtures with purified enzyme contains 100 nM calcineurin, 100 nM calmodulin, and 5 μM 32P-labeled phosphopeptide, in 60 μl (total volume) of assay buffer containing 20 mM Tris (pH 8), 100 mM NaCI, 6 mM MgCl2, 0.5 mM dithiothreitol, 0.1 mg of bovine serum albumin per ml, and either 0.1 mM CaCl2 or 5 mM EGTA. Reaction mixtures with cell lysates contains 20 μl of undiluted lysate, 5 μM 32P-labeled phosphopeptide, and 40 μl of assay buffer. Where indicated, reaction mixtures contains 50 μM peptide 412 or 413 and/or 500 nM okadaic acid, a specific inhibitor of phosphatases 1 and 2A; 500 nM okadaic acid is sufficient for inhibition of Ca2+-independent phosphatases, whereas higher concentrations partially inhibit Ca2+-dependent activity as well. After 15 min at 30°C, reactions are terminated by the addition of 0.5 ml of 100 mM potassium phosphate buffer (pH 7.0) containing 5% trichloroacetic acid. Free inorganic phosphate is isolated by Dowex cation-exchange chromatography and quantitated by scintillation counting as described.

Immunosuppressive agents are dissolved in ethanol at concentrations 1000-fold more than the concentration desired for cell treatments. Cells (106) are suspended in 1 ml of complete medium in microcentrifuge tubes; 1 μl of ethanol or of the ethanolic solution of Cyclosporin A is added, and the cells are incubated at 37°C for 1 hr. Cells are washed twice with 1 ml of PBS on ice and lysed in 50μl of hypotonic buffer containing 50 mM Tris (pH 7.5); 0.1 mM EGTA; 1 mM EDTA; 0.5 mM dithiothreitol; and 50 μg of phenylmethylsulfonyl fluoride, 50 μg of soybean trypsin inhibitor, 5 μg of leupeptin, and 5 μg of aprotinin per ml. Lysates are subjected to three cycles of freezing in liquid nitrogen followed by thawing at 30°C and then are centrifuged at 4°C for 10 min at 12,000×g.(Only for Reference)

59865-13-3

C62H111N11O12

1202.635

环孢菌素;环孢素;Cyclosporine;Cyclosporine A;Ciclosporin

Ethanol:60.1 mg/mL (50 mM)
DMSO:120.3 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years