CAS 59865-13-3|Cyclosporin A

Introduction：Basic information about CAS 59865-13-3|Cyclosporin A, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Cyclosporin A BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Customs
7. Articles494
8. Synonyms

Common Name	Cyclosporin A
CAS Number	59865-13-3	Molecular Weight	1202.611
Density	1.0±0.1 g/cm3	Boiling Point	1293.8±65.0 °C at 760 mmHg
Molecular Formula	C₆₂H₁₁₁N₁₁O₁₂	Melting Point	148-151°C
MSDS	ChineseUSA	Flash Point	736.3±34.3 °C
Symbol	GHS07, GHS08	Signal Word	Danger

Names

Name	cyclosporin A
Synonym	More Synonyms

Cyclosporin A BiologicalActivity

Description	Cyclosporin A is an immunosuppressant which binds to the cyclophilin and inhibits phosphatase activity of calcineurin with an IC50 of 5 nM.
Related Catalog	Signaling Pathways >>Others >>OthersResearch Areas >>Inflammation/Immunology
Target	IC50: 7 nM (calcineurin)
In Vitro	Cyclosporin A is able to bind with the cyclophilin in T cells[1]. Cyclosporin A works by forming a Cyclophilin-Cyclosporin A complex to inhibit calcineurin[2]. Cyclosporin A exhibits inhibitory effect on calcineurin with an IC50 of 7 nM[3]. Cyclosporin A suppresses the nuclear translocation of NF-AT[4]. Cyclosporin A shows an effect on mitochondria via preventing the MTP from opening with an IC50 of 39 nM[5].
In Vivo	Cyclosporin A has immunosuppressive activity, and is active via parenteral and p.o. administration in mice, rat and guinea pigs[6]. Cyclosporin A can be used in organ transplantation to prevent rejection[7].
Kinase Assay	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 NaCl, 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. 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.
Cell Assay	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 50 μL 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.
Animal Admin	Rats are immunized on day 0 i.p. with 0 5 mL and mice i.v. with 0 2 mL of a 10% suspension of washed sheep erythrocytes (SE). To elicit a secondary response, mice are boosted 8-11 weeks after the primary immunization with an i.v. injection of 0-2 mL of 0 25% washed SE (107 cells). For prolonged treatment the animals receive on the average 45 mg/kg cyclosporin A daily in the food during 13 weeks. These rats are immunized 5 days before killing.
References	[1]. Handschumacher RE, et al. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science. 1984 Nov 2;226(4674):544-7. [2]. Liu J, et al. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991 Aug 23;66(4):807-15. [3]. Fruman DA, et al. Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3686-90. [4]. Flanagan WM, et al. Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature. 1991 Aug 29;352(6338):803-7. [5]. Nicolli A, 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 Jan 26;271(4):2185-92. [6]. Borel JF, et al. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977 Jun;32(6):1017-25. [7]. Williams, R, et al. Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group. Lancet, 1994, 344(8920), 423-428.

Chemical & Physical Properties

Density	1.0±0.1 g/cm3
Boiling Point	1293.8±65.0 °C at 760 mmHg
Melting Point	148-151°C
Molecular Formula	C₆₂H₁₁₁N₁₁O₁₂
Molecular Weight	1202.611
Flash Point	736.3±34.3 °C
Exact Mass	1201.841309
PSA	278.80000
LogP	3.35
Vapour Pressure	0.0±0.6 mmHg at 25°C
Index of Refraction	1.468
InChIKey	PMATZTZNYRCHOR-LQJDIJJQSA-N
SMILES	CC=CCC(C)C(O)C1C(=O)NC(CC)C(=O)N(C)CC(=O)N(C)C(CC(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(CC(C)C)C(=O)NC(C)C(=O)NC(C)C(=O)N(C)C(CC(C)C)C(=O)N(C)C(CC(C)C)C(=O)N(C)C(C(C)C)C(=O)N1C
Storage condition	2-8°C
Water Solubility	ethanol: 30 mg/mL

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: GZ4120000

CHEMICAL NAME :: Cyclosporin A

CAS REGISTRY NUMBER :: 59865-13-3

LAST UPDATED :: 199801

DATA ITEMS CITED :: 35

MOLECULAR FORMULA :: C62-H111-N11-O12

MOLECULAR WEIGHT :: 1202.84

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 1911 mg/kg/91W-I

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - coma Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 62500 ug/kg/5D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - other changes Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 20 mg/kg/2D-I

TOXIC EFFECTS :: Behavioral - headache Vascular - acute arterial occlusion Lungs, Thorax, or Respiration - cyanosis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 12 mg/kg

TOXIC EFFECTS :: Vascular - BP elevation not characterized in autonomic section Endocrine - antidiuresis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 30 mg/kg/4D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1480 mg/kg

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 147 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 286 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 24 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2329 mg/kg

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 96 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: >1 gm/kg

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 10 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 140 mg/kg/14D-I

TOXIC EFFECTS :: Endocrine - changes in spleen weight Blood - changes in spleen

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 350 mg/kg/7D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - other changes in urine composition Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - multiple enzyme effects

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 800 mg/kg/10D-I

TOXIC EFFECTS :: Behavioral - food intake (animal) Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 420 mg/kg/28D-I

TOXIC EFFECTS :: Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Musculoskeletal - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 700 mg/kg/28D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - other changes in urine composition

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 210 mg/kg/14D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - renal function tests depressed Kidney, Ureter, Bladder - other changes in urine composition Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other transferases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1200 mg/kg/40D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - other changes in urine composition Biochemical - Metabolism (Intermediary) - amino acids (including renal excretion) Biochemical - Metabolism (Intermediary) - Plasma proteins not involving coagulation

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 140 mg/kg/7D-I

TOXIC EFFECTS :: Vascular - BP elevation not characterized in autonomic section Vascular - regional or general arteriolar or venous dilation

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 60 mg/kg/3D-I

TOXIC EFFECTS :: Vascular - BP elevation not characterized in autonomic section Vascular - structural changes in vessels Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 259 mg/kg/2W-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 166 mg/kg

SEX/DURATION :: male 45 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - other effects on male Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 420 mg/kg

SEX/DURATION :: male 14 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 560 mg/kg

SEX/DURATION :: male 14 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 90 mg/kg

SEX/DURATION :: female 6-8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 50 mg/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intramuscular

DOSE :: 210 mg/kg

SEX/DURATION :: female 14 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Fertility - other measures of fertility

MUTATION DATA

TYPE OF TEST :: Sister chromatid exchange

TEST SYSTEM :: Human Lymphocyte

DOSE/DURATION :: 1 mg/L

REFERENCE :: IGAYAY Igaku No Ayumi. Progress in Medicine. (Ishiyaku Shuppan K.K., 1-7-10, Honkomagom, Bunkyo-ku, Tokyo, Japan) V.1- 1946- Volume(issue)/page/year: 134,403,1985 *** REVIEWS *** IARC Cancer Review:Human Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,77,1990 IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,77,1990 IARC Cancer Review:Group 1 IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,77,1990

Safety Information

Symbol	GHS07, GHS08
Signal Word	Danger
Hazard Statements	H302-H350-H360
Precautionary Statements	P201-P301 + P312 + P330-P308 + P313
Personal Protective Equipment	Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges
Hazard Codes	T:Toxic
Risk Phrases	R45;R60;R22
Safety Phrases	53-45-36/37-24/25-22
RIDADR	NONH for all modes of transport
WGK Germany	3
RTECS	GZ4120000
HS Code	2941909000

Customs

HS Code	2941909000

Articles494

Proteomic analysis in serum of rat hind-limb allograft tolerance induced by immunosuppressive therapy with adipose-derived stem cells.

Plast. Reconstr. Surg. 134(6) , 1213-23, (2014)

Adipose-derived stem cells combined with transient immunosuppression prolonged vascularized composite tissue allotransplant survival and induced immune tolerance in a rodent hind-limb model. The autho...

Differentiation between human ClC-2 and CFTR Cl- channels with pharmacological agents.

Am. J. Physiol. Cell Physiol. 307(5) , C479-92, (2014)

It has been difficult to separate/identify the roles of ClC-2 and CFTR in Cl(-) transport studies. Using pharmacological agents, we aimed to differentiate functionally between ClC-2 and CFTR Cl(-) cha...

The Ca²⁺-calmodulin-Ca²⁺/calmodulin-dependent protein kinase II signaling pathway is involved in oxidative stress-induced mitochondrial permeability transition and apoptosis in isolated rat hepatocytes.

Arch. Toxicol. 88(9) , 1695-709, (2014)

Oxidative stress (OS) is a common event in most hepatopathies, leading to mitochondrial permeability transition pore (MPTP) formation and further exacerbation of both OS from mitochondrial origin and ...

Synonyms

ciclosporin A

sandimmun

Optimmune

cyclosporine A

Atopica

sandimmun neoral

s7481f1

Cyclosporin A

Neoplanta

MFCD00274558

Restasis

Sandimmun optoral

Neoral

Cipol N

ol27-400

EINECS 200-835-2

CyclosporineA

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