Related Searches: Cyclosporin A, Cyclosporin

Cyclosporin A(CAS No. 59865-13-3)

Cyclosporin A C62H111N11O12 (cas 59865-13-3) Molecular Structure

59865-13-3 Structure

Identification and Related Records

【Name】
Cyclosporin A
【Iupac name】
30-ethyl-33-[(E)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,
28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,
4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,
20,23,26,29,32-undecone
【CAS Registry number】
59865-13-3
【Synonyms】
1,11-cyclo[L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-(E)-(2S,3R,4R)-2-amino-3-hydroxy-N,4-dimethyloct-6-enoyl-L-2-aminobutanoyl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucine]
Ciclosporin
Ciclosporinum [INN-Latin]
Cipol N
Cyclo(L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-((3R,4R,6E)-
Cyclosporine
Cyclo(L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-((3R,4R,6E)-6,7-didehydro-3-hydroxy-N,4-dimethyl-L-2-aminooctanoyl-L-2-aminobutanoyl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methylleucyl)
Sang 35
Sandimmune (TN)
S 7481F1
Restasis
30-ethyl-33-(1-hydroxy-2-methyl-hex-4-enyl)-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-dipropan-2-yl-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone
Neoral
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methyl-pent-3-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-3,6,9,18,24-pentakis(2-methylpropyl)-21-propan-2-yl-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone
Sigmasporin Microoral
Cyclo(L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-((3R,4R,6E)-6,7-didehydro-3-hydroxy-N,4-dimethyl-L-2-aminooctanoyl)-L-2-aminobutanoyl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methylleucyl)
Cyclosporin
Consupren
cyclophorine
sandimmun
Sandimmun Neoral
Prestwick_731
Ciclosporin (JP14)
Neoplanta
Neoral (TN)
Sang-35
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methyl-hex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-dipropan-2-yl-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone
Sandimmune
Antibiotic S 7481F1
OL 27-400
【Molecular Formula】
C62H111N11O12 (Products with the same molecular formula)
【Molecular Weight】
1202.61124
【Inchi】
InChI=1S/C62H111N11O12/c1-25-27-28-40(15)52(75)51-56(79)65-43(26-2)58(81)67(18)33-48(74)68(19)44(29-34(3)4)55(78)66-49(38(11)12)61(84)69(20)45(30-35(5)6)54(77)63-41(16)53(76)64-42(17)57(80)70(21)46(31-36(7)8)59(82)71(22)47(32-37(9)10)60(83)72(23)50(39(13)14)62(85)73(51)24/h25,27,34-47,49-52,75H,26,28-33H2,1-24H3,(H,63,77)(H,64,76)(H,65,79)(H,66,78)/b27-25+
【InChIKey】
PMATZTZNYRCHOR-IMVLJIQESA-N
【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
【Isomers 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
【MOL File】
59865-13-3.mol

Chemical and Physical Properties

【Appearance】
White Powder
【Density】
1.016 g/cm3
【Melting Point】
148-151°C
【Boiling Point】
1293.8°C at 760 mmHg
【Flash Point】
736.3°C
【Water】
ethanol: 30 mg/mL
【Solubilities】
ethanol: 30 mg/mL
【Color/Form】
white
【Stability】
No data.
【Storage temp】
2-8°C
【Spectral properties】
Optical rotation: -244 degrees @ 20 deg C (c = 0.6 in chloroform), - 189 degrees @ 20 deg C (c = 0.5 in methanol)
【Computed Properties】
Molecular Weight:1202.61124 [g/mol]
Molecular Formula:C62H111N11O12
XLogP3-AA:7.5
H-Bond Donor:5
H-Bond Acceptor:12
Rotatable Bond Count:15
Tautomer Count:1001
Exact Mass:1201.841368
MonoIsotopic Mass:1201.841368
Topological Polar Surface Area:279
Heavy Atom Count:85
Formal Charge:0
Complexity:2330
Isotope Atom Count:0
Defined Atom Stereocenter Count:0
Undefined Atom Stereocenter Count:12
Defined Bond Stereocenter Count:1
Undefined Bond Stereocenter Count:0
Covalently-Bonded Unit Count:1

Safety and Handling

【Hazard Codes】
T:Toxic
【Risk Statements】
R45;R60;R22
【Safety Statements 】
S53;S45
【Safety】

Hazard Codes?of Cyclosporine (CAS NO.59865-13-3):?ToxicT,HarmfulXn
Risk Statements: 45-60-22-40?
R45: May cause cancer.?
R60: May impair fertility.?
R22: Harmful if swallowed.?
R40: Limited evidence of a carcinogenic effect.
Safety Statements: 53-45-36/37-24/25-22?
S53: Avoid exposure - obtain special instructions before use.?
S45: In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)?
S36/37: Wear suitable protective clothing and gloves.?
S24/25: Avoid contact with skin and eyes.?
S22: Do not breathe dust.
WGK Germany: 3
RTECS: GZ4120000

【Formulations/Preparations】
Neoral is a microemulsion preconcentrate; a microemulsion is a mixture of the lipophilic active substance with accurately balanced amounts of lipophilic solvent, hydrophilic solvent & surfactant. [Nishi Y; Nippon Yakurigaku Zasshi 118 (2): 107-115 (2001)] PubMed Abstract
【Reactivities and Incompatibilities】
Non-PVC containers & administration sets should be used to administer cyclosporine solns. ... Use of glass containers & tubing that does not contain DEHP to administer cyclosporine was recommended.
【Specification】

?Synonyms of Cyclosporin A (CAS NO.59865-13-3) are (R-(R*,R*-(E)))-Cyclic(L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-3-hydroxy-N,4-dimethyl-L-2-amino-6-octenoyl-L-alpha-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl) ;?Abrammune ;?Antibiotic S 7481F1 ;?Arpimune ME ;?CCRIS 1590 ;?Cicloral ;?Cicloral (antibiotic) ;??Cyclo(((E)-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl)-L-2-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl) ;?Cyclo(L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-((3R,4R,6E)-6,7-didehydro-3-hydroxy-N,4-dimethyl-L-2-aminooctanoyl-L-2-aminobutanoyl-N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methylleucyl) ;?Cyclosporin rine ;?DRG-0275 ;?Debio088 ;?Equoral ;?Gengraf ;?HSDB 6881 ;?Imusporin ;?NSC 290193 ;?Neoplanta ;?Neoral ;?OL 27-400 ;?Optimmune ;?Papilock Mini ;?Ramihyphin A ;?Restasis ;?S 7481F1 ;?S-Neoral ;?SDZ-OXL 400 ;?Sandimmun ;?Sandimmun Neoral ;?Sandimmune ;?Sandimmune Neoral ;?Sang 35 ;?Sang-35 ;?Sangcya ;?Sigmasporin Microoral ;?UNII-83HN0GTJ6D ;?Zinograf ME .

【Disposal Methods】

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Use and Manufacturing

【Use and Manufacturing】
Methods of Manufacturing

Lipophilic cyclic undecapeptide isolated from fungi
【Usage】

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.

Biomedical Effects and Toxicity

【Pharmacological Action】
- Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.
- Drugs that are used to treat RHEUMATOID ARTHRITIS.
- Drugs used to treat or prevent skin disorders or for the routine care of skin.
- Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
- Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
【Therapeutic Uses】
Clinical indications for cyclosporine are kidney, liver, heart, & other organ transplantation; rheumatoid arthritis; & psoriasis. ... Cyclosporine usually is used in combination with other agents, especially glucocorticoids & either azathioprine or mycophenolate mofetil &, most recently, sirolimus. ... In rheumatoid arthritis, cyclosporine is used in cases of severe disease that have not responded to methotrexate. Cyclosporine can be used in combination with methotrexate, but the levels of both drugs must be monitored closely. In psoriasis, cyclosporine is indicated for treatment of adult nonimmunocompromised patients with severe & disabling disease who have failed other systemic therapies. Because of its mechanism of action, there is a theoretical bases for the use of cyclosporine in a variety of other T-cell-mediated diseases. Cyclosporine has been reported to be effective in Behcet's acute ocular syndrome, endogenous uveitis, atopic dermatitis, inflammatory bowel disease, & nephrotic syndrome when standard therapies have failed.
For prevention of allograft rejection in adults and children ... .
Cyclosporine is indicated, usually in combination with corticosteroids, for prevention of rejection of renal, hepatic, and cardiac transplants (allografts). /Included in US product labeling/
Cyclosporine is also indicated for prevention of rejection of heart-lung and pancreatic transplants. /NOT included in US product labeling/
Cyclosporine is indicated for treatment of chronic rejection in patients previously treated with other immunosuppressants. /Included in US product labeling/
Cyclosporine is indicated for severe, active, rheumatoid arthritis failing to respond adequately to therapy with methotrexate alone. /Included in US product labeling/
Cyclosporine is indicated for severe, recalcitrant, plaque-type psoriasis failing to respond to at least one systemic therapy or in patients unable to tolerate other systemic therapy. /Included in US product labeling/
Cyclosporine is indicated for prophylaxis and treatment of graft-versus-host disease after bone marrow transplantation. /NOT included in US product labeling/
Cyclosporine is indicated to induce and maintain remissions for steroid-dependent and steroid-resistant nephrotic syndrome due to glomerular diseases. /NOT included in US product labeling/
Data are insufficient to prove that cyclosporine is effective for treatment of generalized pustular or erythrodermic psoriasis.
... This open prospective trial was performed in order to assess the efficacy & safety of cyclosporin A in the treatment of patients with juvenile chronic arthritis (JCA). ... Thirty-four of the patients enrolled were affected by systemic-onset disease & seven by chronic anterior uveitis associated with JCA. The cyclosporin dose was usually 3-5 mg/kg/day. The average duration of therapy was 1.4 yr, with a maximum of 7.2 yr. ... The efficacy of treatment was mainly evident in terms of control of fever & reduction of steroid therapy. The benefits with respect to arthritis, laboratory parameters & uveitis seemed to be less clear-cut. Side-effects were frequent but usually mild or reversible. 66% of the study population withdrew from therapy because of inefficacy or side-effects. Eight systemic patients withdrew from therapy owing to complete remission. ... /It was concluded that/ cyclosporin can be used in the treatment of JCA, its main benefits being the control of fever & a steroid-sparing effect. [Gerloni V et al; Rheumatology 40 (8): 907-913 (2001)]
【Biomedical Effects and Toxicity】
Following oral admin of cyclosporine, the time to peak blood concns is 1.5-2.0 hr. Admin with food both delays & decreases absorption. High & low fat meals consumed within 30 min of admin decr the AUC by approx 13% & the max concn by 33%. This makes it imperative to individualize dosage regimens for outpatients. Cyclosporine is distributed extensively outside the vascular compartment. After iv dosing, the steady-state volume of distribution has been reported to be as high as 3-5 liters/kg in solid-organ transplant recipients. Only 0.1% of cyclosporine is excreted unchanged in urine. ... Cyclosporine & its metabolites are excreted principally through the bile into the feces, with only approx 6% being excreted in the urine. Cyclosporine also is excreted in human milk.
... Absorption of cyclosporine is incomplete following oral admin. The extent of absorption depends upon several variables, including the individual patient & formulation used. The elimination of cyclosporine form the blood is generally biphasic, with a terminal half-life of 5-18 hr. After iv infusion, clearance is approx 5-7 ml/min/kg in adult recipients of renal transplants, but results differ by age & patient populations. For example, clearance is slower in cardiac transplant patients & more rapid in children. The relationship between admin dose & the area under the plasma concn-vs-time curve is linear within the therapeutic range, but the intersubject variability is so large that individual monitoring is required.
Clinicians can administer cyclosporine by continuous iv infusion during the first few days after transplantation, then orally by twice-daily doses, to achieve plasma cyclosporine concns (measured by HPLC) of 75-150 ng/ml (equivalent to whole blood cyclosporine concns of 300-600 ng/ml measured by radioimmunoassay). It appears safe to maintain a trough plasma cyclosporine concn of about 75-150 ng/ml; however, this does not necessarily guarantee safety from nephrotoxicity. Because of preferential distribution of cyclosporine & its metabolites into red blood cells, blood levels are generally higher than plasma levels. When blood cyclosporine levels are 300-600 ng/ml by radioimmunoassay, cerebrospinal fluid levels range from 10-50 ng/ml. The apparent volume of distribution in children under 10 yr of age is about 35 l/kg, & in adults, 4.7 l/kg.
The elimination half-life of an oral cyclosporine dose of 350 mg is 8.9 hr; after a 1400 mg dose, the half-life is 11.9 hr. Elimination occurs predominantly by metab in the liver to form 18-25 metabolites. Metabolites of cyclosporine possess little immunosuppressive activity. Cyclosporine is extensively metabolized in the liver by cytochrome P450IIIA oxidase; however, neurotoxicity & possibly nephrotoxoicity usually correlate with raised blood levels of cyclosporine metabolites. Only 0.1% of a dose ix s excreted unchanged.
Factors known to influence cyclosporine absorption: Time post-transplant; Bile flow; Dietary composition; GI state; Liver function; Small bowel length; Vehicle. /From table/
Different cyclosporine concn zones can exist in plasma due to the temperature dependency in distribution & association, therefore cyclosporine therapeutic & toxic effects may partially be related to these concn zones. [Wu G et al; Med Hypotheses 56 (5): 691-692 (2001)] PubMed Abstract
Sandimmun displays considerable inter- & intra-patient variability because its absorption is bile-dependent & affected by concomitant intake of food. Neoral is a microemulsion preconcentrate; a microemulsion is a mixture of the lipophilic active substance with accurately balanced amounts of lipophilic solvent, hydrophilic solvent & surfactant. As the result of advanced microemulsion technique, Neoral has more consistent & improved absorption characteristics. Cyclosporin (cyclosporin A) has been used as an immunosuppressive agent. [Nishi Y; Nippon Yakurigaku Zasshi 118 (2): 107-115 (2001)] PubMed Abstract

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