Cyclosporine

Base Information

• Chemical Name: Cyclosporine
• CAS No.: 59865-13-3
• Molecular Formula: C62H111N11O12
• Molecular Weight: 1202.63
• Hs Code.: 29419090
• European Community (EC) Number: 611-907-1
• ChEMBL ID: CHEMBL386389
• NCI Thesaurus Code: C406
• NSC Number: 758194,290193
• Pharos Ligand ID: MVACNPGQ9DPR
• RXCUI: 3008
• Wikipedia: Ciclosporin
• Mol file: 59865-13-3.mol

Synonyms:Ciclosporin;CsA Neoral;CsA-Neoral;CsANeoral;CyA NOF;CyA-NOF;Cyclosporin;Cyclosporin A;Cyclosporine;Cyclosporine A;Neoral;OL 27 400;OL 27-400;OL 27400;Sandimmun;Sandimmun Neoral;Sandimmune

Chemical Property of Cyclosporine

Chemical Property:

• Appearance/Colour: White Powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 148-151°C
• Refractive Index: 1.467
• Boiling Point: 1293.8 °C at 760 mmHg
• PKA: 13.32±0.70(Predicted)
• Flash Point: 736.3 °C
• PSA: 278.80000
• Density: 1.016 g/cm³
• LogP: 4.14950
• Storage Temp.: 2-8°C
• Solubility.: ethanol: 30 mg/mL
• Water Solubility.: Soluble in dimethyl sulfoxide and ethanol. Insoluble in water.
• XLogP3: 7.5
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 12
• Rotatable Bond Count: 15
• Exact Mass: 1201.84136802
• Heavy Atom Count: 85
• Complexity: 2330

Purity/Quality:

98% ^*data from raw suppliers

Cyclosporin A ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T， Xn
• Hazard Codes: T,Xn,F
• Statements: 45-60-22-40-36-20/21/22-11
• Safety Statements: 53-45-36/37-24/25-22-26-16

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Chemical Classes: Biological Agents -> Mycotoxins
• Drug Classes: Dermatologic Agents; Transplant Agents
• Canonical SMILES: CCC1C(=O)N(CC(=O)N(C(C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)NC(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N1)C(C(C)CC=CC)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C
• Isomeric SMILES: CCC1C(=O)N(CC(=O)N(C(C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)NC(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N1)C(C(C)C/C=C/C)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C
• Recent ClinicalTrials: Hematopoietic Stem Cell Transplantation in the Treatment of Infant Leukemia
• Recent EU Clinical Trials: A Prospective, Open-label, Multicenter, Randomized Study to Evaluate the Benefits and Risks of Conversion of Existing Adolescent Renal Allograft Recipients Aged 12 to Less Than 18 Years of Age to a Belatacept-based Immunosuppressive Regimen as Compared to Continuation of a Calcineurin Inhibitor-based Regimen, and Their Adherence to Immunosuppressive Medications
• Recent NIPH Clinical Trials: EMaCy trial
• Indications: For prevention of a variety of tissue and organ transplant rejection and treatment of some autoimmune diseases, also used in kidney disease, aplastic anemia, refractory ulcerative colitis. In dermatology, for stubborn and intractable skin diseases, the best effect is severe psoriasis (including vulgaris, pustular, erythrodermic and joint disease); good efficacy on skin disorders including Behcet disease, gangrenous pyoderma, lichen planus, acquired epidermolysis bullosa psychosis; moderate efficacy on disease including alopecia, atopic dermatitis, chronic actinic dermatitis, light class of reticulocyte cell histiocytosis, adult linear IgA bullous dermatitis, pemphigus, bullous pemphigoid (the latter two illness should be in combination with corticosteroids). In addition, Cyclosporine A has effect on systemic lupus erythematosus, dermatomyositis, systemic sclerosis, AIDS, ichthyosis, cutaneous T-cell lymphoma, pityriasis rubra pilaris, generalized missed acrodermatitis, palmoplantar pus blister disease, male pattern baldness, vitiligo, progressive necrotizing xanthogranulomatous, generalized granuloma annulare, lichen myxedema, papular mucin calm disease, hyperthyroidism.
• Drug interactions: 1, In addition to corticosteroids, this product should be avoided in combination with any other immunosuppressive agents. 2, The inactivation of product is mainly in the liver metabolic, any drugs which can affect the liver enzyme activities can affect the metabolism of the product, such as erythromycin, josamycin, doxycycline, ketoconazole, H2 receptor antagonists , calcium antagonists, androgens, oral contraceptives affect activity of cytochrome P-450 liver cell, increase the risk of toxicity of this product. 3, Carbamazepine, phenytoin, phenobarbital, isoniazid, rifampin, et al. can make the plasma concentration of this product decrease. 4, Aminoglycoside antibiotic, trimethoprim-sulfamethoxazole, TMP, amphotericin B, cephalosporins, mechlorethamine, nonsteroidal anti-inflammatory drug, mannitol, furosemide, et al increase nephrotoxicity of cyclosporine . 5, Calcium and increased calcium are disabled when using this product, and cannot be vaccinated. 6, Long-term in combination with glucocorticoid can trigger diabetes, hypertension, ulcer disease and osteoporosis, and can increase the toxicity of this product. 7, Before used Cyclosporin A, other immunosuppressive agents are used, patients have overall decreased immunity and are easy to be infected. Potentially hazardous interactions with other drugs Increased risk of hyperkalaemia with ACE inhibitors, angiotensin-II antagonists, potassiumsparing diuretics, potassium salts. Increased risk of nephrotoxicity with aminoglycosides, amphotericin, co-trimoxazole, disopyramide, foscarnet, melphalan, NSAIDs, polymyxins, quinolones, sulphonamides, thiazide diuretics, trimethoprim and vancomycin. Increased ciclosporin levels with acetazolamide, aciclovir, amiodarone, atazanavir, boceprevir, carvedilol, chloramphenicol, chloroquine, cimetidine, danazol, diltiazem, doxycycline, famotidine, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, glibenclamide, glipizide, grapefruit juice, hydroxychloroquine, imatinib, indinavir, itraconazole, ketoconazole, lercanidipine (concentration of both drugs increased - avoid), macrolides, micafungin, miconazole, high-dose methylprednisolone, metoclopramide, metronidazole, muromonabCD3, nicardipine, posaconazole, progestogens, propafenone, ritonavir, saquinavir and telaprevir (concentration of both drugs increased), tacrolimus, verapamil and voriconazole. Decreased ciclosporin levels with barbiturates, bupropion, carbamazepine, efavirenz, fosphenytoin, griseofulvin, lanreotide, modafinil, octreotide, pasireotide, phenytoin, primidone, quinine, red wine, rifampicin, St John’s wort, sulfadiazine, IV sulfadimidine, sulfasalazine, sulfinpyrazone,terbinafine, ticlopidine and IV trimethoprim and possibly by oxcarbazepine.Aliskiren: concentration of aliskiren increased - avoid. Ambrisentan: concentration of ambrisentan increased. Antibacterials: increased risk of myopathy with daptomycin - try to avoid concomitant use. Anticoagulants: concentration of dabigatran and edoxaban increased - avoid with dabigatran and reduce dose of edoxaban. Antidiabetics: may increase repaglinide concentration, risk of hypoglycaemia. Antimuscarinics: avoid with darifenacin. Antivirals: avoid with simeprevir, increased simeprevir concentration; when starting coadministration with dasubavir and ombitasvir/ paritaprevir/ritonavir, give one fifth of the total daily dose of ciclosporin once daily. Monitor ciclosporin levels and adjust dose and/or dosing frequency as needed. Basiliximab: may alter ciclosporin levels. Bosentan: co-administration of ciclosporin and bosentan is contraindicated. When ciclosporin and bosentan are co-administered, initial trough concentrations of bosentan are 30 times higher than normal. At steady state, trough levels are 3-4 times higher than normal. Blood concentrations of ciclosporin decreased by 50%. Calcium-channel blockers: increased nifedipine concentration and toxicity; amlodipine may increase ciclosporin concentration by up to 40%. Cardiac glycosides: increased digoxin concentration and toxicity. Caspofungin: caspofungin concentration increased - monitor LFTs. Colchicine: risk of myopathy or rhabdomyolysis; also increased blood-ciclosporin concentrations and nephrotoxicity - avoid. Cytotoxics: increased risk of neurotoxicity with doxorubicin; concentration of epirubicin, everolimus and idarubicin increased; reduced excretion of mitoxantrone; increased toxicity with methotrexate; seizures have been reported in bone marrow transplant patients taking busulfan and cyclophosphamide; use crizotinib with caution; concentration of etoposide possibly increased (increased risk of toxicity); possible interaction with docetaxol. Eltrombopag: exposure reduced by ciclosporin. Fidaxomicin: avoid concomitant use.Lenalidomide: concentration of lenalidomide increased. Lipid-lowering agents: absorption reduced by colesevelam, increased risk of myopathy with statins (avoid with simvastatin, max dose of atorvastatin should be 10 mg1 ); avoid with rosuvastatin; increased risk of nephrotoxicity with fenofibrate; bezafibrate may increase creatinine and reduce ciclosporin levels; concentration of both drugs may be increased with ezetimibe. Mycophenolate mofetil: some studies show that ciclosporin decreases plasma MPA AUC levels - no dose change required. NSAIDs: diclofenac concentration increased - reduce diclofenac dose. Omeprazole: may alter ciclosporin concentration. Orlistat: absorption of ciclosporin possibly reduced. Prednisolone: increased prednisolone concentration. Rifaximin: concentration of rifaximin increased. Sirolimus: increased absorption of sirolimus - give sirolimus 4 hours after ciclosporin; sirolimus concentration increased; long term concomitant administration may be associated with deterioration in renal function. Tacrolimus: increased ciclosporin concentration and toxicity - avoid. Ursodeoxycholic acid: unpredictably increased absorption and raised ciclosporin levels in some patients.
• Description: Cyclosporine A is a powerful immunosuppressive drug intended for preventing rejection of kidney, heart, and lung transplants. A new era in the development of immunopharmacology began with the discovery of cyclosporines. Cyclosporines are produced by mycelial mushrooms Tolypocladium inflatum, Tricoderma polysporum, and Cylindrocarpon lucidum, which are found in the ground.Cyclosporine A is the first drug to affect a specific line of protecting cells of the body. Unlike usual cytotoxics, it suppresses T-cells and acts on all cell lines simultaneously. Cyclosporine A significantly eases the ‘reception’ of transplants, and increases the possibility of treating autoimmune system diseases.
• Uses: An immunosuppressant that has revolutionized organ transplantation through its use in the prevention of graft rejection. A group of nonpolar cyclic oligopeptides with immunosupppressant activity. prothrombogenic agent Cyclosporin A is a hydrophobic cyclic peptide isolated from several fungal species including Cylindrocarpon, Fusarium, Trichoderma and Tolypocladium. Cyclosporin A inhibits T-cell activation and has been marketed since 1983 as an immunosuppressant in post-allogeneic organ transplant. Cyclosporin A acts by binding to the protein, cyclophilin (immunophilin), in T-lymphocytes causing inhibition of calcineurin (protein phosphatase 2B). Cyclosporin A reduces transcription of interleukin 2, and inhibits lymphokine production, interleukin release and NO synthesis induced by interleukin 1α, lipopolysaccharides and TNFα.
• Clinical Use: Immunosuppressant: Prophylaxis of solid organ transplant rejection Nephrotic syndrome Atopic dermatitis Psoriasis Rheumatoid arthritis Ulcerative colitis

Technology Process of Cyclosporine

There total 11 articles about Cyclosporine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.5%

→ cyclosporin A (59865-13-3)

Guidance literature:

Reference yield: 55.0%

H-D-Ala-MeLeu-MeLeu-MeVal-MeBmt-Abu-Sar-MeLeu-Val-MeLeu-Ala-SH → cyclosporin A (59865-13-3)

Guidance literature:

With Cyclohexyl isocyanide; benzotriazol-1-ol; In tetrahydrofuran; dichloromethane; at 23 ℃; for 24h; Inert atmosphere;

DOI:10.1021/ja2103372

Reference yield:

7,8-Secocyclosporin-7-carboxylic acid → cyclosporin A (59865-13-3)

Guidance literature:

With Cyclohexyl isocyanide; benzotriazol-1-ol; In tetrahydrofuran; at 70 ℃; for 16h; Inert atmosphere; Microwave irradiation;

DOI:10.1021/ja100517v

upstream raw materials:

C₁₁₇H₂₀₉N₄₁O₂₃

C₆₄H₁₁₃N₁₁O₁₃

C₆₂H₁₀₉N₁₁O₁₄

cyclosporine A

Downstream raw materials:

C₆₂H₁₁₃N₁₁O₁₂

C₆₉H₁₁₅N₁₁O₁₃

C₆₂H₁₀₉N₁₁O₁₄

C₆₂H₁₁₁N₁₁O₁₂

Refernces

• 1、 -. "POLYMER MICELLE COMPOSITION FOR TREATMENT OF RESISTANT CANCER CELLS". . . Retrieved 2011/09/15.
• 2、 -. "Compositions and methods for enhancing drug delivery across and into epithelial tissues". Page column 40; 55. . Retrieved 2010/02/07.