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Identification
NameFlumethasone
Accession NumberDB00663  (APRD00975)
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

Flumethasone is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. As it is a privalate salt, its anti-inflammatory action is concentrated at the site of application. This local effect on diseased areas results in a prompt decrease in inflammation, exudation and itching.

Structure
Thumb
Synonyms
Flumetason
Flumetasona
Flumétasone
Flumetasone
Flumetasonum
External Identifiers
  • RS 2177
  • U 10974
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Locacorten .03%cream.03 %topicalNovartis Pharmaceuticals Canada Inc1966-12-311999-05-19Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CersonRiemser
LocacortenNovartis
LocortenNovartis
TestohgenMaeda Yakuhin
Brand mixtures
NameLabellerIngredients
Locacorten VioformPaladin Labs Inc
Locacorten Vioform EardropsPaladin Labs Inc
LocasalenNovartis Pharmaceuticals Canada Inc
PMS-flumethasone-clioquinolPharmascience Inc
Salts
Name/CASStructureProperties
Flumethasone acetate
ThumbNot applicableDBSALT001651
Flumethasone pivalate
2002-29-1
Thumb
  • InChI Key: JWRMHDSINXPDHB-OJAGFMMFSA-N
  • Monoisotopic Mass: 494.247995294
  • Average Mass: 494.5679
DBSALT001004
Categories
UNIILR3CD8SX89
CAS number2135-17-3
WeightAverage: 410.458
Monoisotopic: 410.190480328
Chemical FormulaC22H28F2O5
InChI KeyWXURHACBFYSXBI-GQKYHHCASA-N
InChI
InChI=1S/C22H28F2O5/c1-11-6-13-14-8-16(23)15-7-12(26)4-5-19(15,2)21(14,24)17(27)9-20(13,3)22(11,29)18(28)10-25/h4-5,7,11,13-14,16-17,25,27,29H,6,8-10H2,1-3H3/t11-,13+,14+,16+,17+,19+,20+,21+,22+/m1/s1
IUPAC Name
(1R,2S,8S,10S,11S,13R,14R,15S,17S)-1,8-difluoro-14,17-dihydroxy-14-(2-hydroxyacetyl)-2,13,15-trimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-3,6-dien-5-one
SMILES
[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[[email protected]](O)[C@@]1(F)[C@@]2([H])C[[email protected]](F)C2=CC(=O)C=C[C@]12C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 21-hydroxysteroids. These are steroids carrying a hydroxyl group at the 21-position of the steroid backbone.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassHydroxysteroids
Direct Parent21-hydroxysteroids
Alternative Parents
Substituents
  • Progestogin-skeleton
  • 21-hydroxysteroid
  • Pregnane-skeleton
  • 20-oxosteroid
  • 3-oxo-delta-1,4-steroid
  • 3-oxosteroid
  • 17-hydroxysteroid
  • 11-hydroxysteroid
  • 11-beta-hydroxysteroid
  • 9-halo-steroid
  • 6-halo-steroid
  • Halo-steroid
  • Oxosteroid
  • Delta-1,4-steroid
  • Alpha-hydroxy ketone
  • Cyclic alcohol
  • Tertiary alcohol
  • Ketone
  • Halohydrin
  • Fluorohydrin
  • Secondary alcohol
  • Cyclic ketone
  • Organofluoride
  • Alcohol
  • Primary alcohol
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organic oxygen compound
  • Alkyl halide
  • Alkyl fluoride
  • Organooxygen compound
  • Organohalogen compound
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of contact dermatitis, atopic dermatitis, exczema, psoriasis, diaper rash and other skin conditions
PharmacodynamicsFlumethasone pivalate is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. As it is a privalate salt, its anti-inflammatory action is concentrated at the site of application. This local effect on diseased areas results in a prompt decrease in inflammation, exudation and itching.
Mechanism of actionFlumethasone is a glucocorticoid receptor agonist. This complex binds to the nucleus causing a variety of genetic activation and repressions. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. 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. Flumethasone binds to plasma transcortin, and it becomes active when it is not bound to transcortin.
Related Articles
AbsorptionMinimal if applied topically
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Primarily hepatic

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityCan lead to signs of irritation such as burning sensation, itching or skin rash at the site of application; hypersensitivity reactions.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9877
Blood Brain Barrier+0.9664
Caco-2 permeable+0.5146
P-glycoprotein substrateSubstrate0.8083
P-glycoprotein inhibitor IInhibitor0.5199
P-glycoprotein inhibitor IINon-inhibitor0.7781
Renal organic cation transporterNon-inhibitor0.8453
CYP450 2C9 substrateNon-substrate0.9008
CYP450 2D6 substrateNon-substrate0.908
CYP450 3A4 substrateSubstrate0.7477
CYP450 1A2 substrateNon-inhibitor0.9087
CYP450 2C9 inhibitorNon-inhibitor0.9052
CYP450 2D6 inhibitorNon-inhibitor0.9591
CYP450 2C19 inhibitorNon-inhibitor0.9337
CYP450 3A4 inhibitorNon-inhibitor0.7935
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9005
Ames testNon AMES toxic0.8008
CarcinogenicityNon-carcinogens0.9259
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4249 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9912
hERG inhibition (predictor II)Non-inhibitor0.6792
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
PackagersNot Available
Dosage forms
FormRouteStrength
Creamtopical.03 %
Creamtopical
Dropsotic
Ointmenttopical
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point219 °C (base only)Not Available
water solubility0.392 mg/LNot Available
logP3.86HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0853 mg/mLALOGPS
logP1.91ALOGPS
logP1.34ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)12.42ChemAxon
pKa (Strongest Basic)-3.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity102.32 m3·mol-1ChemAxon
Polarizability41.25 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Lincoln, F.H., Schneider, W.P. and Spero, G.B.; U.S. Patent 3,557,158; January 19, 1971;
assigned to The Upjohn Co.

General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

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 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 grow...
Gene Name:
NR3C1
Uniprot ID:
P04150
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. Maier C, Runzler D, Schindelar J, Grabner G, Waldhausl W, Kohler G, Luger A: G-protein-coupled glucocorticoid receptors on the pituitary cell membrane. J Cell Sci. 2005 Aug 1;118(Pt 15):3353-61. [PubMed:16079279 ]
  4. Labeur M, Holsboer F: Molecular mechanisms of glucocorticoid receptor signaling. Medicina (B Aires). 2010;70(5):457-62. [PubMed:20920967 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
General Function:
Steroid binding
Specific Function:
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
Gene Name:
SERPINA6
Uniprot ID:
P08185
Molecular Weight:
45140.49 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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23