Cyclosporine A

Biological Activity

Cyclosporin A is an immunosuppressant that binds to cyclophilin and inhibits calcineurin with an IC50 of 7 nM. cyclosporin A [CsA] binds to the cyclophilin 18 (Cyp18)-CsA complex. the Cyp18-CsA complex recruits calcium-regulated neurophosphatase (CaN), leading to the blocking of cytokine gene transcription in activated T cells. CsA is a highly specific inhibitor of T-cell activation.

Product Citations

• 

  J Ethnopharmacol. 2022 Sep 15;295:115409.

  Senegenin alleviates Aβ1-42 induced cell damage through triggering mitophagy
  Cyclosporine A purchased from AbMole

• 

  Stem Cell Rev Rep. 2022 Jun 20.

  Promoting Oligodendrocyte Differentiation from Human Induced Pluripotent Stem Cells by Activating Endocannabinoid Signaling for Treating Spinal Cord Injury
  Cyclosporine A purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Can J Physiol Pharmacol (2014). Figure 2. Cyclosporine A
	Method	MTT assay
	Cell Lines	NRK-52E and LLC-PK1 cells
	Concentrations	10 mg/L
	Incubation Time	24 and 48 h
	Results	A noticeably higher susceptibility of the rat kidney cell line to toxicity in the presence of CyA in vehicle was noted compared with the pig kidney cell line

	Source	Can J Physiol Pharmacol (2014). Figure 1. Cyclosporine A
	Method	Hepatocytes
	Cell Lines	NL and HL rat
	Concentrations	2.5 mg/L
	Incubation Time	5 and 30 min
	Results	In the hepatocytes exposed to CyA–2% NL rat serum, there was an initial spike in the uptake of CyA by the cells regardless of pretreatment

Protocol (for reference only)

Cell Experiment
Cell lines	Jurkat cells (clone J77)
Preparation method	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.
Concentrations	~100 nM
Incubation time	1 h

Animal Experiment
Animal models	Rat
Formulation	0.5% solution of tragacanth
Dosages	45 mg/kg
Administration	oral

Chemical Information

Molecular Weight	1202.61
Formula	C62H111N11O12
CAS Number	59865-13-3
Solubility (25°C)	DMSO ≥ 45 mg/mL
Storage	2-8°C, dry, sealed, protect from light

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Goksu Erol et al. Drug Chem Toxicol. The protective effects of omega 3 fatty acids and sesame oil against cyclosporine A-induced nephrotoxicity.

[2] Borel JF, et al. Immunology. Effects of the new anti-lymphocytic peptide cyclosporin A in animals.