CyclicPepedia Knowledge Base
Cyclosporine
Basic information
| CPKB ID | CP00459 |
| IUPAC Name | (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-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 |
| Synonyms |
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| Source |
Tolypocladium inflatum [Division : Plants and Fungi]
Taxonomy :29910 (Fungi-Ascomycota-Hypocreales-Sordariomycetes-Ophiocordycipitaceae Tolypocladium) Wikipedia: Tolypocladium inflatum Trichoderma polysporum [Division : Plants and Fungi]
Taxonomy :40695 (Fungi-Ascomycota-Hypocreales-Sordariomycetes-Hypocreaceae Trichoderma) Wikipedia: Trichoderma polysporum PubChem |
| Family | |
| Function |
Anti-Asthmatic Anti-Coronaviral Anti-Fungal Anti-Rheumatic Immunomodulatory PubChem |
| Information |
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed). A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed). A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed). |
Legend
Structure
| Molecular Formula |
C62H111N11O12 |
| Molecular Weight | 1201.841368 g/mol |
| SMILES | C/C=C/C[C@@H](C)[C@@H](O)[C@H]1C(=O)N[C@@H](CC)C(=O)N(C)CC(=O)N(C)[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C)C(=O)N(C)[C@@H](CC(C)C)C(=O)N(C)[C@@H](CC(C)C)C(=O)N(C)[C@@H](C(C)C)C(=O)N1C |
| 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+/t40-,41+,42-,43+,44+,45+,46+,47+,49+,50+,51+,52-/m1/s1 |
| InChIKey | PMATZTZNYRCHOR-HXPUBHAINA-N |
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2D Structure
PubChem|5284373
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Sequence
| IUPAC Condensed | cyclo[Abu-Sar-N(Me)Leu-Val-N(Me)Leu-Ala-D-Ala-N(Me)Leu-N(Me)Leu-N(Me)Val-N(Me)Bmt(E)] |
| Amino acid chain | Abu(1)--Sar--N(Me)Leu--Val--N(Me)Leu--Ala--D-Ala--N(Me)Leu--N(Me)Leu--N(Me)Val--N(Me)Bmt(E)(1) |
| Graph representation | Abu,Sar,N(Me)Leu,Val,N(Me)Leu,Ala,D-Ala,N(Me)Leu,N(Me)Leu,N(Me)Val,N(Me)Bmt(E) @0,10 |
| One letter code from Structure | LVLAALLVTAG |
| Amino acid chain from Structure | Abu(1)--NMe-Gly--NMe-Leu--Val--NMe-Leu--Ala--Ala--NMe-Leu--NMe-Leu--NMe-Val--NMe-Bmt(1) |
| Description of the conversion sequence | The one letter code and Amino acid chain derived from the structural transformation may be inconsistent, with the Amino acid chain containing Essential Amino acid and the one letter code not. |
| svg Image |
Structure Properties
| Property Name | Property Value | |
|---|---|---|
| Exact Mass | 1201.841368 | |
| Number of Rings | 1.0 | |
| Complexity | 0.458823529 | |
| XlogP3 AA | 3.269 | |
| Heavy Atom Count | 85.0 | |
| Hydrogen Bond Donor Count | 5.0 | |
| Hydrogen Bond Acceptor Count | 12.0 | |
| Rotatable Bond Count | 15.0 |
| Property Name | Property Value | |
|---|---|---|
| Formal Charge | 0.0 | |
| Refractivity | 328.4446 | |
| Rule_of_Five | 0.0 | |
| Number of Atoms | 85.0 | |
| Topological Polar Surface Area | 278.8 | |
| Refractivity | 328.4446 | |
| Veber Rule | 0.0 | |
| Ghose Filter | 0.0 |
| Property Name | Property Value | |
|---|---|---|
| RDKit Fingerprint |
01000000001000100100100011011000110000000011000000100010100001101100110101111100100000010010110010000110000001001000001010110000010000000010110100011101100010010110001010010100000110000110101111000000001001001000000100000000010001000100111100000010011100111011000111001000000010000001000000000001011000011010101111000000010100010000001011011000010000000010101001000000010000000000111001001010010100000000000110011110000010100000100000101001100010000101000100010010011000000100000000001010000110011101110001100101110101100000011010011101001100100000100010010100001001011110010010001001001010110100101100100001001010011100011000001111000101100110000011100111000000000110001000100000010101011100011100100010000101100000000100101010001000000001100000011010001101110000101100010000000001100001001000001000001110001000000100000001110001000000010011001100001000010010000100101011000100100000111001001011001100000000111000000110010110011000000001011110100010001001011001010000011000010011011010010001110100010100000000100000001010001011000100110011100000000010000000000100001101100001010000001001110010001001100001010010000010100000000111001001010000010100001000101000101110100100101101010001010000011010000001001100110101100100000111100000011100010010011110000000100100001110100000000000100010100000000001011001110111100001000100101101100000010001110100000001010001110011010000010000100100010000001100000001110101001100101000100101100011000000011010001111001000001011001101000100010000100001100000010111011000000000100100100111000011110000001000010000001100100100010011101000000100100011011001000101100010000001000000100011000000000010100000010011000000000010010011000001100010000100000010000001000000010000011100100100100000000001000010000000101000100011001110000001010010010000100010000000000000010101101000001001111101000100000011011010011010100110010000000110100000000010010000100000010000011001101100000100101101000000010010110101000010000110000110010010110001111011000011010001001101100000100101001100100000000000000011101001100100100100010000010011 |
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| Morgan Fingerprint |
0100010000100000000100000000000001000010000000010000000000000000000000000000000010000000001000100000010000000000000100000100001000001100000000000000000000000000000000100000000000000000001000000000001000000000100000000001000000010000000000000000000000100100000000000000010000000000000101000000001010000100000000000010000000000000000010010000000000000100000010000000000000100000000000000000000000000000000000000000000000000000000000100000000000000000000000000000000000000001000010000010000000001000000000000000000000000000000000000000000000001000000000001000000000000000000000000000000000000100000010000000000000000000000000000000000000000010000000000010000010000000010001000001000000000100000000100000000000000000000000000000010000000000000000010000010000000000010000000000000000000000000000000000001000000001000000000000000100100000000000000000100000000000000000000000000000000010000000000000010000000000000000000000000100100010000000110000000000000000000000000000000000000000000000001000000000000000000000000000000000010000 |
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| MACCS Keys |
00000000000000000000000000000000000000000000000000000110000000000000000000110001000001100111110101011000100010110011110011100001100110001101111100101111111111111100110 |
Sequence Properties
| Property Name | Property Value | |
|---|---|---|
| Boman Index | -2.8690909090909 | |
| Instability | 1.37272727272727 | |
| Charge | -0.00201570060725275 | |
| Aliphatic Index | 221.818181818181 |
Binding Target
Detail
Uniprot: Q96LZ3
Kind: Protein>Calcineurin b homologous proteins
Organism: Homo sapiens(Human)
Evidevce: DrugBank
Sequence: MGNEASYPAEMCSHFDNDEIKRLGRRFKKLDLDKSGSLSVEEFMSLPELRHNPLVRRVIDVFDTDGDGEVDFKEFILGTSQFSVKGDEEQKLRFAFSIYDMDKDGYISNGELFQVLKMMVGNNLTDWQLQQLVDKTIIILDKDGDGKISFEEFSAVVRDLEIHKKLVLIV
General Function:
Calcium ion binding
Specific Function:
Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity (By similarity).
Additional database information: TTD[Calcineurin subunit B type 2]
Detail
Uniprot: P49069
Kind: Protein>
Organism: Homo sapiens(Human)
Evidevce: DrugBank
Sequence: MESMAVATDGGERPGVPAGSGLSASQRRAELRRRKLLMNSEQRINRIMGFHRPGSGAEEESQTKSKQQDSDKLNSLSVPSVSKRVVLGDSVSTGTTDQQGGVAEVKGTQLGDKLDSFIKPPECSSDVNLELRQRNRGDLTADSVQRGSRHGLEQYLSRFEEAMKLRKQLISEKPSQEDGNTTEEFDSFRIFRLVGCALLALGVRAFVCKYLSIFAPFLTLQLAYMGLYKYFPKSEKKIKTTVLTAALLLSGIPAEVINRSMDTYSKMGEVFTDLCVYFFTFIFCHELLDYWGSEVP
General Function:
Likely involved in the mobilization of calcium as a result of the TCR/CD3 complex interaction. Binds to cyclophilin B.
Specific Function:
Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (PubMed:23041287, PubMed:24392163, PubMed:27226539). Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol (PubMed:23041287, PubMed:24392163, PubMed:27226539). Required for the stability of GET1 (PubMed:32187542). Stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium (PubMed:7522304). Essential for the survival of peripheral follicular B cells (By similarity)
Additional database information: TTD[Calcium signal-modulating cyclophilin ligand]
Detail
Uniprot: P62937
Kind: Protein>Peptidyl-prolyl isomerase
Organism: Homo sapiens(Human)
Evidevce: DrugBank
Sequence: MGNEASYPAEMCSHFDNDEIKRLGRRFKKLDLDKSGSLSVEEFMSLPELRHNPLVRRVIDVFDTDGDGEVDFKEFILGTSQFSVKGDEEQKLRFAFSIYDMDKDGYISNGELFQVLKMMVGNNLTDWQLQQLVDKTIIILDKDGDGKISFEEFSAVVRDLEIHKKLVLIV
General Function:
Virion binding
Specific Function:
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Additional database information: TTD[Peptidyl-prolyl cis-trans isomerase A]
Detail
Uniprot: P30405
Kind: Protein>Peptidyl-prolyl isomerase
Organism: Homo sapiens(Human)
Evidevce: DrugBank
Sequence: MLALRCGSRWLGLLSVPRSVPLRLPAARACSKGSGDPSSSSSSGNPLVYLDVDANGKPLGRVVLELKADVVPKTAENFRALCTGEKGFGYKGSTFHRVIPSFMCQAGDFTNHNGTGGKSIYGSRFPDENFTLKHVGPGVLSMANAGPNTNGSQFFICTIKTDWLDGKHVVFGHVKEGMDVVKKIESFGSKSGRTSKKIVITDCGQLS
General Function:
Peptidyl-prolyl cis-trans isomerase activity
Specific Function:
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.
Additional database information: TTD[Peptidyl-prolyl cis-trans isomerase F]
Biologic Description
Drug Indication PubChem|5284373
Cyclosporine is approved for a variety of conditions. Firstly, it is approved for the prophylaxis of organ rejection in allogeneic kidney, liver, and heart transplants. It is also used to prevent bone marrow transplant rejection. For the above indications, cyclosporine can be used in conjunction with azathioprine and corticosteroids. Finally, cyclosporine can be used in patients who have chronic transplant rejection and have received previous immunosuppressive therapy and to prevent or treat graft-versus-host disease (GVHD).Secondly, cyclosporine is used for the treatment of patients with severe active rheumatoid arthritis (RA) when they no longer respond to methotrexate alone. It can be used for the treatment of adult non-immunocompromised patients with severe, recalcitrant, plaque psoriasis that have failed to respond to at least one systemic therapy or when systemic therapies are not tolerated or contraindicated. The ophthalmic solution of cyclosporine is indicated to increase tear production in patients suffering from keratoconjunctivitis sicca. In addition, cyclosporine is approved for the treatment of steroid dependent and steroid-resistant nephrotic syndrome due to glomerular diseases which may include minimal change nephropathy, focal and segmental glomerulosclerosis or membranous glomerulonephritis.A cyclosporine ophthalmic emulsion is indicated in the treatment of vernal keratoconjunctivitis in adults and children.Off-label, cyclosporine is commonly used for the treatment of various autoimmune and inflammatory conditions such as atopic dermatitis, blistering disorders, ulcerative colitis, juvenile rheumatoid arthritis, uveitis, connective tissue diseases, as well as idiopathic thrombocytopenic purpura.
Pharmacology PubChem|5284373
Cyclosporine exerts potent immunosuppressive actions on T cells, thereby prolonging survival following organ and bone marrow transplants. This drug prevents and controls serious immune-mediated reactions including allograft rejection, graft versus host disease, and inflammatory autoimmune disease.Some notable effects of cyclosporine are hypertrichosis, gingival hyperplasia, and hyperlipidemia. There is also some debate about this drug causing nephrotoxicity.
Toxicity PubChem|5284373
The oral LD50 in rats is 1480 mg/kg and the TDLO in humans is 12 mg/kg. **Overdose information** In cases of overdose with oral cyclosporine, forced emesis and gastric lavage are recommended 2 hours after ingestion. There are little data available in the literature regarding overdoses with cyclosporine, but hepatotoxicity and nephrotoxicity may occur. One case report of an cyclosporine overdose due to medical error was made involving a 26 year old female and noted the occurrence of nausea, flushing, tremor, vertigo and vomiting, which resolved within about 1 day. Anorexia and a feeling of increased body girth were also experienced by this patient and resolved within about 2 weeks. When overdose with cyclosporine is observed, it is important to consider that dialysis and charcoal, hemoperfusion are not effective techniques to remove cyclosporine from the body.
Metabolism PubChem|5284373
Cyclosporine is metabolized in the intestine and the liver by CYP450 enzymes, predominantly CYP3A4 with contributions from CYP3A5. The involvement of CYP3A7 is not clearly established. Cyclosporine undergoes several metabolic pathways and about 25 different metabolites have been identified. One of its main active metabolites, AM1, demonstrates only 10-20% activity when compared to the parent drug, according to some studies. The 3 primary metabolites are M1, M9, and M4N, which are produced from oxidation at the 1-beta, 9-gamma, and 4-N-demethylated positions, respectively.
Manufacturers
| Manufacturers Name | Value | |
|---|---|---|
| CreativePeptides | ||
| Bayer healthcare pharmaceuticals | ||
| Upsher smith laboratories | ||
| Merck |
| Manufacturers Name | Value | |
|---|---|---|
| Apotex | ||
| Baxter Healthcare Corp | ||
| Pharmasources | ||
| Novartis | ||
| AstraZeneca |
Forecasting tools
| Forecasting tools | Value | |
|---|---|---|
| Structure to Sequence | ||
| Structure Properties | ||
| Sequence to Structure | ||
| Sequence Properties | ||
| Expasy ProtParam Tool | LVLAALLVTAG | |
| SEA | RUN SEA Predictions |
Information Source
| Property Name | Property ID | |
|---|---|---|
| Patents | PMATZTZNYRCHOR-HXPUBHAINA-N | |
| pubchem | 5284373 | |
| Drugbank | DB00091 | |
| DRAMP3 | ||
| Uniprot | ||
| Cybase | ||
| CONOSERVER | ||
| BindingDB | BDBM50022815 | |
| CHEMBL | CHEMBL160 | |
| CTD | D016572 | |
| Wikipedia | Ciclosporin | |
| KEGG Compound/Drug | C05086 | |
| CHEBI | CHEBI:92233 | |
| EPA DSSTox | DTXSID0020365 | |
| FDA Global Substance Registration System (GSRS) | 83HN0GTJ6D | |
| DTP/NCI | ||
| Chemspider | 4447449 | |
| VARIDT | DR00448 | |
| INTEDE | DR0321 | |
| TheMarker | D2K0WC |
Reference
| Pubmed_ID | Title | DOI | Journal | |
|---|---|---|---|---|
18207736 |
10.1016/j.bmcl.2007.12.062. | Bioorg Med Chem Lett |
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Novel echinocandin antifungals. Part 1: novel side-chain analogs of the natural product FR901379Abstract
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18424132 |
10.1016/j.bmcl.2008.03.093. | Bioorg Med Chem Lett |
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Novel echinocandin antifungals. Part 2: Optimization of the side chain of the natural product FR901379. Discovery of micafunginAbstract
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19393553 |
10.1016/j.jbiosc.2009.01.002. | J Biosci Bioeng |
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Improvement of FR901379 production by mutant selection and medium optimizationAbstract
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