cyclosporin A   Click here for help

GtoPdb Ligand ID: 1024

Synonyms: ciclosporin | cyclosporine | cyclosporine A | Ikervis® (opthalmic solution) | Neoral® | Sandimmun® | Verkazia® (opthalmic solution)
Approved drug Immunopharmacology Ligand
cyclosporin A is an approved drug (FDA and UK (1983), EMA (2015))
Compound class: Peptide
Comment: Originally isolated from Tolypocladium inflatum, cyclosporin A acts as a calcineurin inhibitor.
There is some ambiguity in the literature as to the exact stereochemistry of cyclosporin A. Other common representations on PubChem are CID 5280754, and CID 24883466.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: cyclosporin a

cyclosporin A is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CC=CCC(C(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(=O)NC(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N1C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)O)C
Isomeric SMILES C/C=C/C[C@H]([C@H]([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(=O)N[C@@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N1C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)O)C
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
InChI Key PMATZTZNYRCHOR-CGLBZJNRSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Dong Z, Ekins S, Polli JE. (2013)
Structure-activity relationship for FDA approved drugs as inhibitors of the human sodium taurocholate cotransporting polypeptide (NTCP).
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2. Fehrenbach T, Cui Y, Faulstich H, Keppler D. (2003)
Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins.
Naunyn Schmiedebergs Arch Pharmacol, 368 (5): 415-20. [PMID:14530907]
3. Fruman DA, Klee CB, Bierer BE, Burakoff SJ. (1992)
Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A.
Proc Natl Acad Sci USA, 89 (9): 3686-90. [PMID:1373887]
4. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P. (2012)
Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
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5. Kim RB, Leake B, Cvetkovic M, Roden MM, Nadeau J, Walubo A, Wilkinson GR. (1999)
Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity.
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6. Kuo J, Bobardt M, Chatterji U, Mayo PR, Trepanier DJ, Foster RT, Gallay P, Ure DR. (2019)
A Pan-Cyclophilin Inhibitor, CRV431, Decreases Fibrosis and Tumor Development in Chronic Liver Disease Models.
J Pharmacol Exp Ther, 371 (2): 231-241. [PMID:31406003]
7. Liu J, Farmer Jr JD, Lane WS, Friedman J, Weissman I, Schreiber SL. (1991)
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes.
Cell, 66 (4): 807-15. [PMID:1715244]
8. Ozvegy C, Litman T, Szakács G, Nagy Z, Bates S, Váradi A, Sarkadi B. (2001)
Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells.
Biochem Biophys Res Commun, 285 (1): 111-7. [PMID:11437380]
9. Porter Jr GA, Beutner G. (2018)
Cyclophilin D, Somehow a Master Regulator of Mitochondrial Function.
Biomolecules, 8 (4). [PMID:30558250]
10. Treiber A, Schneiter R, Häusler S, Stieger B. (2007)
Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil.
Drug Metab Dispos, 35 (8): 1400-7. [PMID:17496208]
11. Yamamoto Y, Kanazawa T, Shimamura M, Ueki M, Hazato T. (1997)
Inhibitory effects of spinorphin, a novel endogenous regulator, on chemotaxis, O2- generation, and exocytosis by N-formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophils.
Biochem Pharmacol, 54 (6): 695-701. [PMID:9310346]