Identification

Name
Amcinonide
Accession Number
DB00288  (APRD00788)
Type
Small Molecule
Groups
Approved
Description

Amcinonide is a corticosteroid. [Wikipedia]

Structure
Thumb
Synonyms
  • Amcinonida
  • Amcinonidum
  • Triamcinolonacetatcyclopentanonid
External IDs
CL 34699 / CL-34699
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CyclocortOintment1 mg/1gTopicalDPT Laboratories, Ltd.1999-02-122006-01-31Us
CyclocortCream0.1 %TopicalGlaxosmithkline Inc1996-09-12Not applicableCanada
CyclocortLotion0.1 %TopicalGlaxosmithkline Inc1996-09-12Not applicableCanada
CyclocortOintment0.1 %TopicalGlaxosmithkline Inc1997-01-20Not applicableCanada
Cyclocort Crm 0.1%Cream.1 %TopicalLederle Cyanamid Canada Inc.1978-12-311997-01-29Canada
Cyclocort Lot 0.1%Lotion.1 %TopicalLederle Cyanamid Canada Inc.1983-12-311997-01-29Canada
Cyclocort Ont 0.1%Ointment.1 %TopicalLederle Cyanamid Canada Inc.1983-12-311997-01-29Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmcinonideOintment1 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.2003-03-19Not applicableUs
AmcinonideLotion1 mg/1gTopicalE. Fougera & CO., A division of Fougera Pharmaceuticals Inc.2002-11-06Not applicableUs
AmcinonideOintment1 mg/1gTopicalE. Fougera & CO., A division of Fougera Pharmaceuticals Inc.2014-04-03Not applicableUs
AmcinonideCream1 mg/1gTopicalE. Fougera & CO., A division of Fougera Pharmaceuticals Inc.2003-05-15Not applicableUs
AmcinonideCream1 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.2002-05-31Not applicableUs
Ratio-amcinonideLotion0.1 %TopicalTeva2004-05-06Not applicableCanada
Ratio-amcinonideOintment0.1 %TopicalTeva2004-05-05Not applicableCanada
Ratio-amcinonideCream0.1 %TopicalTeva2003-09-18Not applicableCanada
Taro-amcinonideCream0.1 %TopicalTaro Pharmaceuticals, Inc.2003-02-13Not applicableCanada
Taro-amcinonideOintment0.1 %TopicalTaro Pharmaceuticals, Inc.Not applicableNot applicableCanada
International/Other Brands
Mycoderm / Penticort / Visderm
Categories
UNII
423W026MA9
CAS number
51022-69-6
Weight
Average: 502.5717
Monoisotopic: 502.236681679
Chemical Formula
C28H35FO7
InChI Key
ILKJAFIWWBXGDU-MOGDOJJUSA-N
InChI
InChI=1S/C28H35FO7/c1-16(30)34-15-22(33)28-23(35-26(36-28)9-4-5-10-26)13-20-19-7-6-17-12-18(31)8-11-24(17,2)27(19,29)21(32)14-25(20,28)3/h8,11-12,19-21,23,32H,4-7,9-10,13-15H2,1-3H3/t19-,20-,21-,23+,24-,25-,27-,28+/m0/s1
IUPAC Name
2-[(1'S,2'S,4'R,8'S,9'S,11'S,12'R,13'S)-12'-fluoro-11'-hydroxy-9',13'-dimethyl-16'-oxo-5',7'-dioxaspiro[cyclopentane-1,6'-pentacyclo[10.8.0.0²,⁹.0⁴,⁸.0¹³,¹⁸]icosane]-14',17'-dien-8'-yl]-2-oxoethyl acetate
SMILES
[H][C@@]12C[C@@]3([H])[C@]4([H])CCC5=CC(=O)C=C[C@]5(C)[C@@]4(F)[C@@H](O)C[C@]3(C)[C@@]1(OC1(CCCC1)O2)C(=O)COC(C)=O

Pharmacology

Indication

For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.

Associated Conditions
Pharmacodynamics

Amcinonide is a topical corticosteroid. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and antipruritic agents. Amcinonide reduces or inhibits the actions of chemicals in the body that cause inflammation, redness, and swelling. The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man. When in an ointment form, amcinonide also helps the skin maintain moisture.

Mechanism of action

The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. Amcinonide has affinity for the glucocorticoid receptor. It has weak affinity for the progesterone receptor, and virtually no affinity for the mineralocorticoid, estrogen, or androgen receptors.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
UAnnexin A1
agonist
Human
Absorption

Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys.

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

Results from acute toxicity studies do not indicate that any risk of acute intoxication is to be expected following a single dermal application of an overdose (application over a large area under conditions favorable to absorption) or inadvertent oral ingestion.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Schultz, W., Sieger, G.M. and Krieger, C.: British Patent 1,442,925; July 14,1976; assigned to American Cyanamid Company.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014433
KEGG Drug
D01387
PubChem Compound
443958
PubChem Substance
46506705
ChemSpider
392009
ChEBI
31199
ChEMBL
CHEMBL1200732
Therapeutic Targets Database
DAP001044
PharmGKB
PA164746074
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Amcinonide
ATC Codes
D07AC11 — Amcinonide
AHFS Codes
  • 84:06.00 — Anti-inflammatory Agents
FDA label
Download (143 KB)
MSDS
Download (48.1 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Altana inc
  • Taro pharmaceutical industries ltd
  • Astellas pharma us inc
Packagers
  • DPT Laboratories Ltd.
  • E. Fougera and Co.
  • Nycomed Inc.
  • Physicians Total Care Inc.
  • Taro Pharmaceuticals USA
Dosage forms
FormRouteStrength
CreamTopical1 mg/1g
LotionTopical1 mg/1g
OintmentTopical1 mg/1g
CreamTopical.1 %
LotionTopical.1 %
OintmentTopical.1 %
LotionTopical0.1 %
OintmentTopical0.1 %
CreamTopical0.1 %
Prices
Unit descriptionCostUnit
Amcinonide 0.1% Cream 60 gm Tube84.29USD tube
Amcinonide 0.1% Ointment 60 gm Tube84.29USD tube
Amcinonide 0.1% Cream 30 gm Tube28.71USD tube
Amcinonide 0.1% Cream 15 gm Tube20.99USD tube
Amcinonide 0.1% cream1.68USD g
Cyclocort 0.1 % Cream0.62USD g
Cyclocort 0.1 % Ointment0.62USD g
Cyclocort 0.1 % Lotion0.52USD g
Ratio-Amcinonide 0.1 % Ointment0.33USD g
Ratio-Amcinonide 0.1 % Cream0.29USD g
Taro-Amcinonide 0.1 % Cream0.29USD g
Ratio-Amcinonide 0.1 % Lotion0.27USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00774 mg/mLALOGPS
logP3.16ALOGPS
logP3.2ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)13.63ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area99.13 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity127.88 m3·mol-1ChemAxon
Polarizability52.23 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9643
Blood Brain Barrier+0.9897
Caco-2 permeable-0.5844
P-glycoprotein substrateSubstrate0.7713
P-glycoprotein inhibitor IInhibitor0.7198
P-glycoprotein inhibitor IIInhibitor0.5596
Renal organic cation transporterNon-inhibitor0.7608
CYP450 2C9 substrateNon-substrate0.8615
CYP450 2D6 substrateNon-substrate0.9016
CYP450 3A4 substrateSubstrate0.7307
CYP450 1A2 substrateNon-inhibitor0.8688
CYP450 2C9 inhibitorNon-inhibitor0.8732
CYP450 2D6 inhibitorNon-inhibitor0.8982
CYP450 2C19 inhibitorNon-inhibitor0.9188
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8999
Ames testNon AMES toxic0.8886
CarcinogenicityNon-carcinogens0.941
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4315 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9488
hERG inhibition (predictor II)Non-inhibitor0.5298
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-024i-3891000000-ef24dafd204a6e82ead7

Taxonomy

Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 11-beta-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Alpha-acyloxy ketones / Ketals / 1,3-dioxolanes / Fluorohydrins / Cyclic ketones
show 9 more
Substituents
Progestogin-skeleton / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 9-halo-steroid / Halo-steroid / Hydroxysteroid / Oxosteroid / 11-beta-hydroxysteroid / 11-hydroxysteroid
show 27 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
acetate ester, spiroketal, 11beta-hydroxy steroid, 20-oxo steroid, fluorinated steroid, 3-oxo-Delta(1),Delta(4)-steroid, corticosteroid (CHEBI:31199)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
  3. 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:16891588]
  4. 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:16895953]
  5. Hammer F, Stewart PM: Cortisol metabolism in hypertension. Best Pract Res Clin Endocrinol Metab. 2006 Sep;20(3):337-53. [PubMed:16980198]
  6. 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:17038445]
  7. 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:17086345]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Structural molecule activity
Specific Function
Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Play...
Gene Name
ANXA1
Uniprot ID
P04083
Uniprot Name
Annexin A1
Molecular Weight
38713.855 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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:17016423]
  3. Serres M, Comera C, Schmitt D: Annexin 1 regulation in human epidermal cells. Cell Mol Biol (Noisy-le-grand). 1994 Jul;40(5):701-6. [PubMed:7981624]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Monograph [Link]
  2. Cyclocort monograph [Link]

Drug created on June 13, 2005 07:24 / Updated on December 10, 2018 13:39