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Identification
Name Cortisone acetate
Accession Number DB01380
Type small molecule
Groups approved
Description

Cortisone acetate is a steroid hormone that has both glucocoriticoid and mineral corticoid activities. Corticosteroids are used to provide relief for inflamed areas of the body. They lessen swelling, redness, itching, and allergic reactions. They are often used as part of the treatment for a number of different diseases, such as severe allergies or skin problems, asthma, or arthritis. Endogenous glucocorticoids and some synthetic corticoids have high affinity to the protein transcortin (also called CBG, corticosteroid-binding protein), whereas all of them bind albumin. Glucocorticoids also bind to the cytosolic glucocorticoid receptor.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names Not Available
Brand name mixtures Not Available
Categories
  • Anti-inflammatory Agents
  • Corticosteroid
CAS number 50-04-4
Weight Average: 402.4807
Monoisotopic: 402.204238692
Chemical Formula C23H30O6
InChI Key InChIKey=ITRJWOMZKQRYTA-RFZYENFJSA-N
InChI
InChI=1S/C23H30O6/c1-13(24)29-12-19(27)23(28)9-7-17-16-5-4-14-10-15(25)6-8-21(14,2)20(16)18(26)11-22(17,23)3/h10,16-17,20,28H,4-9,11-12H2,1-3H3/t16-,17-,20+,21-,22-,23-/m0/s1
Plain Text
IUPAC Name
2-[(1S,2R,10S,11S,14R,15S)-14-hydroxy-2,15-dimethyl-5,17-dioxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-14-yl]-2-oxoethyl acetate
SMILES
[H][C@@]12CC[C@](O)(C(=O)COC(C)=O)[C@@]1(C)CC(=O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Ethers
  • Alcohols and Polyols
  • Cyclohexenes and Derivatives
  • Ketones
Pharmacology
Indication For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders.
Pharmacodynamics As a glucocorticoid agent, cortisone acetate changes genetic transcription levels causing varied metabolic effects and a modified immune response to varied stimuli. lucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated.
Mechanism of action Cortisone acetate binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-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 the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Route of elimination Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.
Half life Not Available
Clearance Not Available
Toxicity Side effects include inhibition of bone formation, suppression of calcium absorption, delayed wound healing and hyperglycemia.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
  • Watson laboratories inc
  • Merck and co inc
  • Barr laboratories inc
  • Elkins sinn div ah robins co inc
  • Everylife
  • Heather drug co inc
  • Impax laboratories inc
  • Inwood laboratories inc sub forest laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lannett co inc
  • Panray corp sub ormont drug and chemical co inc
  • Purepac pharmaceutical co
  • Vitarine pharmaceuticals inc
  • West ward pharmaceutical corp
  • Whiteworth towne paulsen inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Cortisone acetate powder 24.18 USD g
Cortisone Acetate 25 mg Tablet 0.47 USD tablet
Cortisone 25 mg tablet 0.46 USD tablet
Cortaid 1% cream 0.21 USD g
CVS Pharmacy cortisone 1% cream 0.18 USD g
CVS Pharmacy anti-itch 1% cream 0.13 USD g
Hydrocortisone 0.5% cream 0.11 USD g
Medi-cortisone 1% cream 0.1 USD g
Patents Not Available
Properties
State solid
Melting point 222 oC
Experimental Properties
Property Value Source
water solubility 0.02 mg/mL at 25 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)] PhysProp
logP 2.10 [HANSCH,C ET AL. (1995)] PhysProp
Predicted Properties
Property Value Source
water solubility 2.78e-02 g/l ALOGPS
logP 2.35 ALOGPS
logP 2.10 ChemAxon Molconvert
logS -4.16 ALOGPS
pKa 15.41 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 97.74 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 105.63 ChemAxon Molconvert
polarizability 43.25 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00973 Link_out
KEGG Compound C08173 Link_out
PubChem Compound 5745 Link_out
PubChem Substance 46508852 Link_out
ChemSpider 5543 Link_out
PharmGKB PA449131 Link_out
Drug Product Database 280437 Link_out
RxList http://www.rxlist.com/cgi/generic/cortisne.htm Link_out
Drugs.com http://www.drugs.com/cdi/cortisone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Cortisone_acetate Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (74.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Glucocorticoid receptor

Pharmacological action: yes
Actions: agonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth

Organism class: human
UniProt ID: P04150 Link_out
Gene: NR3C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Grossman R, Yehuda R, Golier J, McEwen B, Harvey P, Maria NS: Cognitive effects of intravenous hydrocortisone in subjects with PTSD and healthy control subjects. Ann N Y Acad Sci. 2006 Jul;1071:410-21. Pubmed
  2. Rautanen A, Eriksson JG, Kere J, Andersson S, Osmond C, Tienari P, Sairanen H, Barker DJ, Phillips DI, Forsen T, Kajantie E: Associations of body size at birth with late-life cortisol concentrations and glucose tolerance are modified by haplotypes of the glucocorticoid receptor gene. J Clin Endocrinol Metab. 2006 Nov;91(11):4544-51. Epub 2006 Aug 8. Pubmed
  3. Hammer F, Stewart PM: Cortisol metabolism in hypertension. Best Pract Res Clin Endocrinol Metab. 2006 Sep;20(3):337-53. Pubmed
  4. Shaw JR, Gabor K, Hand E, Lankowski A, Durant L, Thibodeau R, Stanton CR, Barnaby R, Coutermarsh B, Karlson KH, Sato JD, Hamilton JW, Stanton BA: Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic. Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R1052-60. Epub 2006 Oct 12. Pubmed
  5. Sher L: Combined dexamethasone suppression-corticotropin-releasing hormone stimulation test in studies of depression, alcoholism, and suicidal behavior. ScientificWorldJournal. 2006 Oct 31;6:1398-404. Pubmed
  6. Schlechte JA, Ginsberg BH, Sherman BM: Regulation of the glucocorticoid receptor in human lymphocytes. J Steroid Biochem. 1982 Jan;16(1):69-74. Pubmed
  7. Schlechte JA, Sherman BM: Decreased glucocorticoid receptor binding in adrenal insufficiency. J Clin Endocrinol Metab. 1982 Jan;54(1):145-9. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. Pubmed
Comments
Drug created on July 06, 2007 14:32 / Updated on December 26, 2010 09:01

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.