Details of the Drug

General Information of Drug (ID: DMAZJFX)

Drug Name
Ciclosporin
Synonyms
Ciclosporin; Ciclosporin (Ciclosporin A); Ciclosporina; Ciclosporina [INN-Spanish]; Ciclosporine; Ciclosporine [INN-French]; Ciclosporinum; Ciclosporinum [INN-Latin]; Cipol N; Consupren; Cyclosporin; Cyclosporine A; Equoral; Antibiotic S 7481F1; Gengraf; Neoplanta; Neoral; Ramihyphin A; Restasis; S-Neoral; Sandimmun; Sandimmun Neoral; Sandimmune; Sang 35; Sang-35; SangCyA; Sigmasporin Microoral; cyclosporin A; cyclosporine; 59865-13-3; 83HN0GTJ6D; CHEBI:4031; CSA; DSSTox_CID_365; DSSTox_RID_75541; MFCD00274558; MLS001333756; UNII-83HN0GTJ6D
Indication
Disease Entry ICD 11 Status REF
Graft-versus-host disease 4B24 Approved [1]
Psoriasis vulgaris EA90 Approved [2]
Brain injury NA07.Z Phase 4 [3]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [4]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [4]
Xerophthalmia 5B55.Y Investigative [2]
⏷ Show the Full List of Indication(s)
Affected Organisms
Humans and other mammals
ATC Code
L04AD01: Ciclosporin
L04AD: Calcineurin inhibitors
L04A: IMMUNOSUPPRESSANTS
L04: IMMUNOSUPPRESSANTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
L04AD01: Ciclosporin
L04AD: Calcineurin inhibitors
L04A: IMMUNOSUPPRESSANTS
L04: IMMUNOSUPPRESSANTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
S01XA18: Ciclosporin
S01XA: Other ophthalmologicals
S01X: OTHER OPHTHALMOLOGICALS
S01: OPHTHALMOLOGICALS
S: SENSORY ORGANS
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski): 4 Molecular Weight (mw) 1202.6
Logarithm of the Partition Coefficient (xlogp) 7.5
Rotatable Bond Count (rotbonds) 15
Hydrogen Bond Donor Count (hbonddonor) 5
Hydrogen Bond Acceptor Count (hbondacc) 12
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1-8 h [5]
Bioavailability
The bioavailability of drug is 30% [5]
Clearance
The clearance of drug is 22.5 L/h [6]
Elimination
Cyclosporine excretion is primarily biliary with only 3-6% of the dose (including the parent drug and metabolites) excreted in the urine while 90% of the administered dose is eliminated in the bile [5]
Half-life
The concentration or amount of drug in body reduced by one-half in 19 hours [6]
Metabolism
The drug is metabolized via the liver [5]
Vd
The volume of distribution (Vd) of drug is 4-8 L/kg [7]
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Bone density decreased Not Available BGLAP OTK1YLWQ [8]
Haemolysis Not Available VWF OTNMMA2P [8]
Nephropathy toxic Not Available PPP3R1 OTGQNFJQ [8]
Thrombosis Not Available GNAQ OTOODWTU [8]
Chemical Identifiers
Formula
C62H111N11O12
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
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
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-CGLBZJNRSA-N
Cross-matching ID
PubChem CID
5284373
ChEBI ID
CHEMBL160
CAS Number
59865-13-3
UNII
83HN0GTJ6D
DrugBank ID
DB00091
INTEDE ID
DR0321
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Calcineurin (PPP3CA) TTA4LDE PP2BA_HUMAN Inhibitor [2]
HUMAN cyclophilin D (CYP3) TT95SAZ PPIF_HUMAN Inhibitor [4]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [9]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [10]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [12]
Cytochrome P450 3A5 (CYP3A5)
Main DME 		DEIBDNY CP3A5_HUMAN Substrate [13]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Substrate [14]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
(3R)-3-hydroxyacyl-CoA dehydrogenase (HSD17B8) OTX1DWEF DHB8_HUMAN Gene/Protein Processing [15]
(E3-independent) E2 ubiquitin-conjugating enzyme OTHGS2VA UBE2O_HUMAN Gene/Protein Processing [16]
(Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4) OTQK3M9X ABHD4_HUMAN Gene/Protein Processing [16]
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1) OTG2T749 CP24A_HUMAN Gene/Protein Processing [17]
1,4-alpha-glucan-branching enzyme (GBE1) OTK2N05B GLGB_HUMAN Gene/Protein Processing [18]
1-acyl-sn-glycerol-3-phosphate acyltransferase alpha (AGPAT1) OTX65INE PLCA_HUMAN Gene/Protein Processing [16]
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2) OT5I4Y9K PLCB_HUMAN Gene/Protein Processing [16]
1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon (AGPAT5) OTNY3VMD PLCE_HUMAN Gene/Protein Processing [16]
1-acyl-sn-glycerol-3-phosphate acyltransferase gamma (AGPAT3) OTAUR5TG PLCC_HUMAN Gene/Protein Processing [16]
1-acylglycerol-3-phosphate O-acyltransferase ABHD5 (ABHD5) OTY829Z3 ABHD5_HUMAN Gene/Protein Processing [16]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Graft-versus-host disease
ICD Disease Classification 4B24
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Calcineurin (PPP3CA) DTT PPP3CA 5.29E-01 1.74E-03 9.99E-03
P-glycoprotein 1 (ABCB1) DTP P-GP 2.00E-01 2.57E-02 6.18E-02
Breast cancer resistance protein (ABCG2) DTP BCRP 6.07E-04 1.66E-01 4.54E-01
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 7.41E-21 4.03E-01 1.33E+00
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 5.05E-02 4.52E-01 5.39E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 8.67E-01 -3.83E-03 -1.24E-02
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2 Cyclosporine and tacrolimus for the treatment of rheumatoid arthritis. Curr Opin Rheumatol. 2007 May;19(3):238-45.
3 ClinicalTrials.gov (NCT00332462) A Study to Evaluate the Efficiency of Intravenously Administered Cyclosporine in de Novo Liver Transplant Recipients. U.S. National Institutes of Health.
4 Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020 Mar;19(3):149-150.
5 Sargentini-Maier ML, Espie P, Coquette A, Stockis A: Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects. Drug Metab Dispos. 2008 Jan;36(1):36-45. Epub 2007 Oct 1.
6 Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs. 1993 Jun;45(6):953-1040. doi: 10.2165/00003495-199345060-00007.
7 Cyclosporine Product Label
8 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
9 Is cyclosporine A transport inhibited by pravastatin via multidrug resistant protein 2? Eur J Clin Pharmacol. 2010 Feb;66(2):153-8.
10 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
11 Contribution of down-regulation of intestinal and hepatic cytochrome P450 3A to increased absorption of cyclosporine A in a rat nephrosis model. J Pharmacol Exp Ther. 2008 Nov;327(2):592-9.
12 Dasatinib significantly reduced in vivo exposure to cyclosporine in a rat model: The possible involvement of CYP3A induction. Pharmacol Rep. 2019 Apr;71(2):201-205.
13 CYP3A4*18B and CYP3A5*3 polymorphisms contribute to pharmacokinetic variability of cyclosporine among healthy Chinese subjects. Eur J Pharm Sci. 2015 Aug 30;76:238-44.
14 CYP3A7, CYP3A5, CYP3A4, and ABCB1 genetic polymorphisms, cyclosporine concentration, and dose requirement in transplant recipients. Ther Drug Monit. 2008 Dec;30(6):689-99.
15 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
16 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
17 Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
18 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.