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Showing drug card for Ciclesonide (DB01410)

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Version 2.5
Creation Date 2007-07-17 12:38:14
Update Date 2009-02-19 16:04:38
Primary Accession Number DB01410
Secondary Accession Number Not Available
Name Ciclesonide
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Ciclesonide is a glucocorticoid used to treat obstructive airway diseases. It is marketed under the brand name Alvesco.
Synonyms
  1. ciclesonide
Brand Names
  1. Alvesco
Brand Mixtures Not Available
Chemical IUPAC Name Not Available
Chemical Formula C32H44O7
Chemical Structure Structure
CAS Registry Number 141845-82-1
InChI Identifier InChI=1/C32H44O7/c1-18(2)28(36)37-17-25(35)32-26(38-29(39-32)19-8-6-5-7-9-19)15-23-22-11-10-20-14-21(33)12-13-30(20,3)27(22)24(34)16-31(23,32)4/h12-14,18-19,22-24,26-27,29,34H,5-11,15-17H2,1-4H3/t22-,23-,24-,26+,27+,29?,30-,31-,32+/m0/s1
InChI Key LUKZNWIVRBCLON-FOMURGDPBY
KEGG Drug D01703 Link Image
KEGG Compound Not Available
PubChem Compound 444033 Link Image
PubChem Substance 10299472 Link Image
ChEBI ID Not Available
PharmGKB ID Not Available
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02285606 Link Image
RxList Link http://www.rxlist.com/cgi/generic/omnaris.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Ciclesonide Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 540.6876
Monoisotopic Molecular Weight 540.3087
State Solid
Melting Point Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 1.57e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP 4.08 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -5.54 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(C)C(=O)OCC(=O)[C@@]12O[C@@H](O[C@@H]1C[C@H]1[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@H]3[C@@H](O)C[C@]21C)C1CCCCC1
Canonical SMILES CC(C)C(=O)OCC(=O)C12OC(OC1CC1C3CCC4=CC(=O)C=CC4(C)C3C(O)CC21C)C1CCCCC1
Drug Category
  • Anti-Allergic Agents
  • Glucocorticoids
ATC Codes
AHFS Codes
  • 68:04.00
Indication For the treatment of nasal symptoms associated with seasonal and perennial allergic rhinitis in adults and adolescents 12 years of age and older.
Pharmacology Ciclesonide is a pro-drug that is enzymatically hydrolyzed to a pharmacologically active metabolite, C21-desisobutyryl-ciclesonide (des-ciclesonide or RM1) following intranasal application. Des-ciclesonide has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120 times higher than the parent compound. The precise mechanism through which ciclesonide affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic inflammation.
Mechanism of Action Glucocorticoids such as ciclesonide can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of glucocorticoids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Ciclesonide reduces inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins. Ciclesonide is a glucocorticoid receptor agonist. On binding, the corticoreceptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing an increase or decrease in expression of specific target genes, including suppression of IL2 (interleukin 2) expression.
Absorption Ciclesonide and des-ciclesonide have negligible oral bioavailability (both less than 1%) due to low gastrointestinal absorption and high first-pass metabolism. The intranasal administration of ciclesonide at recommended doses results in negligible serum concentrations of ciclesonide.
Toxicity Not Available
Protein Binding The percentage of ciclesonide and des-ciclesonide bound to human plasma proteins averaged ≥ 99% each, with ≤ 1% of unbound drug detected in the systemic circulation.
Biotransformation Des-ciclesonide undergoes metabolism in the liver to additional metabolites mainly by the cytochrome P450 (CYP) 3A4 isozyme and to a lesser extent by CYP 2D6.
Half Life Not Available
Dosage Forms
Form Route
Aerosol, metered Nasal
Aerosol, metered Respiratory (inhalation)
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Itraconazole Increased effects/toxicity of ciclesonide
Ketoconazole Increased effects/toxicity of ciclesonide
Nelfinavir Increased effects/toxicity of ciclesonide
Ritonavir Increased effects/toxicity of ciclesonide
Food Interactions Not Available
Pathways Not Available
General References
  1. Mutch E, Nave R, McCracken N, Zech K, Williams FM: The role of esterases in the metabolism of ciclesonide to desisobutyryl-ciclesonide in human tissue. Biochem Pharmacol. 2007 May 15;73(10):1657-64. Epub 2007 Jan 28. [PubMed Link Image]
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
  2. Cytochrome P450 2D6 (CYP2D6)
Targets
  1. Corticosteroid-binding globulin
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 2D6 (CYP2D6)
Enzyme 2 Gene Name CYP2D6
Enzyme 2 SwissProt ID P10635 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P10635|CP2D6_HUMAN Cytochrome P450 2D6 (EC 1.14.14.1) 
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGMTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
Drug Target 1 [top]
Target 1 ID 232
Target 1 Name Corticosteroid-binding globulin
Target 1 Synonyms
  1. CBG
  2. Corticosteroid-binding globulin precursor
  3. Serpin A6
  4. Transcortin
Target 1 Gene Name SERPINA6
Target 1 Protein Sequence >Corticosteroid-binding globulin precursor 
MPLLLYTCLLWLPTSGLWTVQAMDPNAAYVNMSNHHRGLASANVDFAFSLYKHLVALSPK
KNIFISPVSISMALAMLSLGTCGHTRAQLLQGLGFNLTERSETEIHQGFQHLHQLFAKSD
TSLEMTMGNALFLDGSLELLESFSADIKHYYESEVLAMNFQDWATASRQINSYVKNKTQG
KIVDLFSGLDSPAILVLVNYIFFKGTWTQPFDLASTREENFYVDETTVVKVPMMLQSSTI
SYLHDSELPCQLVQMNYVGNGTVFFILPDKGKMNTVIAALSRDTINRWSAGLTSSQVDLY
IPKVTISGVYDLGDVLEEMGIADLFTNQANFSRITQDAQLKSSKVVHKAVLQLNEEGVDT
AGSTGVTLNLTSKPIILRFNQPFIIMIFDHFTWSSLFLARVMNPV
Target 1 Number of Residues 411
Target 1 Molecular Weight 45141
Target 1 Theoretical pI 5.94
Target 1 GO Classification
Function
enzyme regulator activity
enzyme inhibitor activity
protease inhibitor activity
endopeptidase inhibitor activity
serine-type endopeptidase inhibitor activity
Process
Not Available
Component
Not Available
Target 1 General Function Involved in serine-type endopeptidase inhibitor activity
Target 1 Specific Function Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-22
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 179971 Link Image
Target 1 UniProtKB/Swiss-Prot ID P08185 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name CBG_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Secreted protein
Target 1 Gene Sequence >1218 bp 
ATGCCACTCCTCCTGTACACCTGTCTTCTCTGGCTGCCCACCAGCGGCCTCTGGACCGTC
CAGGCCATGGATCCTAACGCTGCTTATGTGAACATGAGTAACCATCACCGGGGCCTGGCT
TCAGCCAACGTTGACTTTGCCTTCAGCCTGTATAAGCACCTAGTGGCCTTGAGTCCCAAA
AAGAACATTTTCATCTCCCCTGTGAGCATCTCCATGGCCTTAGCTATGCTGTCCCTGGGC
ACCTGTGGCCACACACGGGCCCAGCTTCTCCAGGGCCTGGGTTTCAACCTCACTGAGAGG
TCTGAGACTGAGATCCACCAGGGTTTCCAGCACCTGCACCAACTCTTTGCAAAGTCAGAC
ACCAGCTTAGAAATGACTATGGGCAATGCCTTGTTTCTTGATGGCAGCCTGGAGTTGCTG
GAGTCATTCTCAGCAGACATCAAGCACTACTATGAGTCAGAGGTCTTGGCTATGAATTTC
CAGGACTGGGCAACAGCCAGCAGACAGATCAACAGCTATGTCAAGAATAAGACACAGGGG
AAAATTGTCGACTTGTTTTCAGGGCTGGATAGCCCAGCCATCCTCGTCCTGGTCAACTAT
ATCTTCTTCAAAGGCACATGGACACAGCCCTTTGACCTGGCAAGCACCAGGGAGGAGAAC
TTCTATGTGGACGAGACAACTGTGGTGAAGGTGCCCATGATGTTGCAGTCGAGCACCATC
AGTTACCTTCATGACTCAGAGCTCCCCTGCCAGCTGGTGCAGATGAACTACGTGGGCAAT
GGGACTGTCTTCTTCATCCTTCCGGACAAGGGGAAGATGAACACAGTCATCGCTGCACTG
AGCCGGGACACGATTAACAGGTGGTCCGCAGGCCTGACCAGCAGCCAGGTGGACCTGTAC
ATTCCAAAGGTCACCATCTCTGGAGTCTATGACCTTGGAGATGTGCTGGAGGAAATGGGC
ATTGCAGACTTGTTCACCAACCAGGCAAATTTCTCACGCATCACCCAGGACGCCCAGCTG
AAGTCATCAAAGGTGGTCCATAAAGCTGTGCTGCAACTCAATGAGGAGGGTGTGGACACA
GCTGGCTCCACTGGGGTCACCCTAAACCTGACGTCCAAGCCTATCATCTTGCGTTTCAAC
CAGCCCTTCATCATCATGATCTTCGACCACTTCACCTGGAGCAGCCTTTTCCTGGCGAGG
GTTATGAACCCAGTGTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID SERPINA6 Link Image
Target 1 GenAtlas ID SERPINA6 Link Image
Target 1 HGNC ID HGNC:1540 Link Image
Target 1 Chromosome Location 14
Target 1 Locus 14q32.1
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Emptoz-Bonneton A, Cousin P, Seguchi K, Avvakumov GV, Bully C, Hammond GL, Pugeat M: Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity. J Clin Endocrinol Metab. 2000 Jan;85(1):361-7. [PubMed Link Image]
  2. Smith CL, Power SG, Hammond GL: A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol. J Steroid Biochem Mol Biol. 1992 Aug;42(7):671-6. [PubMed Link Image]
  3. Hammond GL, Smith CL, Goping IS, Underhill DA, Harley MJ, Reventos J, Musto NA, Gunsalus GL, Bardin CW: Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5153-7. [PubMed Link Image]
  4. Kato EA, Hsu BR, Kuhn RW: Comparative structural analyses of corticosteroid binding globulin. J Steroid Biochem. 1988 Feb;29(2):213-20. [PubMed Link Image]
  5. Bardin CW, Gunsalus GL, Musto NA, Cheng CY, Reventos J, Smith C, Underhill DA, Hammond G: Corticosteroid binding globulin, testosterone-estradiol binding globulin, and androgen binding protein belong to protein families distinct from steroid receptors. J Steroid Biochem. 1988;30(1-6):131-9. [PubMed Link Image]
  6. Van Baelen H, Power SG, Hammond GL: Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93. Steroids. 1993 Jun;58(6):275-7. [PubMed Link Image]
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.