生物活性

• 描述Cyclosporin A is an immunosuppressant which binds to its receptor cyclophilin (CyP) by forming drug-dependent complexes to inhibit the activity of calmodulin-dependent phosphatase calcineurin (IC50=7 nM)^[1]. Cyclosporin A appears to specifically inhibit the early events of T lymphocyte activation by blocking the transcription of NF-AT, which is essential for early T-cell gene activation^[2]. Moreover, it has been demonstrated that Cyclosporin A can inhibit nitric oxide synthesis induced by interleukin-alpha, lipopolysaccharide and NF-κB. Nanomolar concentrations of Cyclosporin A (IC50 = 39 nM) displays an inhibition of the permeability transition pore (MTP) opening of an inner membrane channel in Mammalian mitochondria^[3]. Studies in animals indicate that Cyclosporin A can induce apoptosis of rat lymphocytes and mouse B-cell lymphoma cell line WEHI-231. Notably, Cyclosporin A was found to be widely used for treating rejecting of allogenic transplant to prevent the activity of the patient's immune system^[4]. It has been studied in transplants of skin, kidney, liver, small intestine, bone marrow and so on.
• 作用机制Cyclosporin A is a calcineurin inhibitor that exerts its immunosuppressive effects via the formation of cyclosporin A-cyclophilin complex.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  A2780/ADR cells	-	Function assay	-	Inhibition of P-glycoprotein expressed in A2780/ADR cells by calcein AM assay， IC50=1.41254 μM	17890094
  african green monkey Vero cells	-	Function assay	24 h	Antiviral activity against West Nile virus infected in african green monkey Vero cells assessed as decrease in viral RNA synthesis after 24 hrs by luciferase reporter gene assay, IC50=8 μM	19451286
  CK1 cells	-	Function assay	-	Antiviral activity against HPV-33 infected in CK1 cells assessed as inhibition of viral replication after 7 days, TC50=0.3 μM	18212100

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• 动物研究
  剂量	Mice: 5 mg/kg - 15 mg/kg[5] (i.p.) Rat: 10 mg/kg[6] (s.c.)
  给药途径	i.p., s.c.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01268995	New Onset Diabetes Mellitus Af... more >>ter Renal Transplantation Collapse <<	Phase 2	Terminated(It was impossible t... more >>o recruit the scheduled number of patients) Collapse <<	-	Austria ... more >> Medical University of Vienna/General Hospital Vienna, Austria, A-1090 Collapse <<
  NCT02328963	Transplantation Infection ... more >> Cytomegalovirus Infection Collapse <<	Phase 4	Completed	-	France ... more >> CHU de Bordeaux Bordeaux, France, 33000 CHU La Cavale Blanche Brest, France, 29609 CHRU Caen - Hôpital de Caen Caen, France, 14033 CHU de Limoges - Hôpital Dupuytren Limoges, France Hôpital Edouard Herriot Lyon, France, 69003 APHP - Hôpital Necker Paris, France, 75015 APHP - Kremlin Bicetre Paris, France, 94275 CHRU Strasbourg Strasbourg, France CHU de Toulouse - Hôpital Rangueil Toulouse, France, 31000 Collapse <<
  NCT00821587	-	-	Completed	-	-

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• 参考文献

• [1] Handschumacher RE, Harding MW, et al. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science. 1984;226(4674):544-7.

  [2] Flanagan WM, Corthesy B, et al. Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature. 1991;352(6338):803-7.

  [3] Nicolli A, Basso E, et al. Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, and cyclosporin A-sensitive channel. J Biol Chem. 1996;271(4):2185-92.

  [4] Emmel EA, Verweij CL, et al. Pillars Article: Cyclosporin A Specifically Inhibits Function of Nuclear Proteins Involved in T Cell Activation. Science. 1989. 246: 1617-1620. J Immunol. 2018;201(11):3149-3152.