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Identification
NameFlumethasone Pivalate
Accession NumberDB00663  (APRD00975)
TypeSmall Molecule
GroupsApproved
Description

Flumethasone 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.

Structure
Thumb
Synonyms
SynonymLanguageCode
FlumetasonGermanINN
FlumetasonaSpanishINN
FlumétasoneFrenchINN
Flumetasone pivalateNot AvailableNot Available
FlumetasonumLatinINN
Salts
Name/CAS Structure Properties
Flumetasone Pivalate
Thumb Not applicable DBSALT001004
Brand names
NameCompany
CersonRiemser
LocacortenNovartis
LocortenNovartis
TestohgenMaeda Yakuhin
Brand mixtures
Brand NameIngredients
FlumetanolClioquinol + Flumethasone Pivalate
FlusalicFlumethasone Pivalate + Salicylic Acid
FlusanFlumethasone Pivalate + Salicylic Acid
Locacorten VioformClioquinol + Flumethasone Pivalate
Locacorten Vioform CreamClioquinol + Flumethasone Pivalate
Locacorten Vioform EardropsClioquinol + Flumethasone Pivalate
LocasalenFlumethasone Pivalate + Salicylic Acid
LosalenFlumethasone Pivalate + Salicylic Acid
TopisalenFlumethasone Pivalate + Salicylic Acid
CategoriesNot Available
CAS number2002-29-1
WeightAverage: 494.5679
Monoisotopic: 494.247995294
Chemical FormulaC27H36F2O6
InChI KeyJWRMHDSINXPDHB-OJAGFMMFSA-N
InChI
InChI=1S/C27H36F2O6/c1-14-9-16-17-11-19(28)18-10-15(30)7-8-24(18,5)26(17,29)20(31)12-25(16,6)27(14,34)21(32)13-35-22(33)23(2,3)4/h7-8,10,14,16-17,19-20,31,34H,9,11-13H2,1-6H3/t14-,16+,17+,19+,20+,24+,25+,26+,27+/m1/s1
IUPAC Name
2-[(1R,2S,8S,10S,11S,13R,14R,15S,17S)-1,8-difluoro-14,17-dihydroxy-2,13,15-trimethyl-5-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-dien-14-yl]-2-oxoethyl 2,2-dimethylpropanoate
SMILES
C[C@@H]1C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]2(C)[C@@]1(O)C(=O)COC(=O)C(C)(C)C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassGluco/mineralocorticoids, Progestogins and Derivatives
Direct parentGluco/mineralocorticoids, Progestogins and Derivatives
Alternative parentsHalogenated Steroids; Ketosteroids; Hydroxysteroids; Iridoids and Derivatives; Cyclohexanols; Tertiary Alcohols; Cyclic Alcohols and Derivatives; Ketones; Fluorohydrins; Carboxylic Acid Esters; Ethers; Polyamines; Enolates; Organofluorides; Alkyl Fluorides; Aldehydes
Substituents11-hydroxy-steroid; 20-keto-steroid; 9-halo-steroid; 6-halo-steroid; 17-hydroxy-steroid; 3-keto-steroid; 11-noriridane monoterpene; monoterpene; cyclohexanol; tertiary alcohol; cyclic alcohol; fluorohydrin; carboxylic acid ester; secondary alcohol; halohydrin; ketone; enolate; carboxylic acid derivative; polyamine; ether; organohalogen; organofluoride; alcohol; carbonyl group; alkyl halide; alkyl fluoride; aldehyde
Classification descriptionThis compound belongs to the gluco/mineralocorticoids, progestogins and derivatives. These are steroids whose structure is based on an hydroxylated prostane moiety.
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.
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
Property Value Probability
Human Intestinal Absorption + 0.9877
Blood Brain Barrier + 0.9664
Caco-2 permeable + 0.5146
P-glycoprotein substrate Substrate 0.8083
P-glycoprotein inhibitor I Inhibitor 0.5199
P-glycoprotein inhibitor II Non-inhibitor 0.7781
Renal organic cation transporter Non-inhibitor 0.8453
CYP450 2C9 substrate Non-substrate 0.9008
CYP450 2D6 substrate Non-substrate 0.908
CYP450 3A4 substrate Substrate 0.7477
CYP450 1A2 substrate Non-inhibitor 0.9087
CYP450 2C9 substrate Non-inhibitor 0.9052
CYP450 2D6 substrate Non-inhibitor 0.9591
CYP450 2C19 substrate Non-inhibitor 0.9337
CYP450 3A4 substrate Non-inhibitor 0.7935
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9005
Ames test Non AMES toxic 0.8008
Carcinogenicity Non-carcinogens 0.9259
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.4249 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9912
hERG inhibition (predictor II) Non-inhibitor 0.6792
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
PackagersNot Available
Dosage formsNot Available
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 Solubility0.0107ALOGPS
logP3.21ALOGPS
logP3.58ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)12.44ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area100.9 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity125.17 m3·mol-1ChemAxon
Polarizability50.96 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot 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 ReferenceNot Available
External Links
ResourceLink
KEGG DrugD01464
PubChem Compound443980
PubChem Substance46505121
ChemSpider392021
ChEBI31620
ChEMBLCHEMBL1200877
Therapeutic Targets DatabaseDAP000814
PharmGKBPA164749388
Drug Product Database5134
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Glucocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Glucocorticoid receptor P04150 Details

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
  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
  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
  4. Labeur M, Holsboer F: Molecular mechanisms of glucocorticoid receptor signaling. Medicina (B Aires). 2010;70(5):457-462. Pubmed

Carriers

1. Corticosteroid-binding globulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Corticosteroid-binding globulin P08185 Details

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
  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
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 23, 2014 15:12