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Identification
NameClocortolone
Accession NumberDB00838  (APRD00877)
TypeSmall Molecule
GroupsApproved
Description

Clocortolone is a medium potency corticosteroid that is often used as a topical cream for the relief of inflammatory oand pruritic (itching) arising from steroid-responsive dermatoses of the scalp.

Structure
Thumb
Synonyms
SynonymLanguageCode
9-chloro-6alpha-Fluoro-11beta,21-dihydroxy-16alpha-methyl-1,4-pregnadien-3,20-dioneNot AvailableNot Available
9-chloro-6alpha-Fluoro-16alpha-methyl-1,4-pregnadiene-11beta,21-diol-3,20-dioneNot AvailableNot Available
ClocortolonGermanINN
ClocortolonaSpanishINN
ClocortoloneFrenchINN
ClocortolonumLatinINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Clodermcream.001 g/gtopicalCoria Laboratories1977-08-22Not AvailableUs
Clodermcream.001 g/gtopicalPromius Pharma, LLC1977-08-22Not AvailableUs
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixtures
Brand NameIngredients
KabanClocortolone and Clocortolone caproate
KabanimatClocortolone and Clocortolone caproate
Salts
Name/CASStructureProperties
Clocortolone trimethylacetate
ThumbNot applicableDBSALT000939
Categories
CAS number34097-16-0
WeightAverage: 410.907
Monoisotopic: 410.166015296
Chemical FormulaC22H28ClFO4
InChI KeyYMTMADLUXIRMGX-RFPWEZLHSA-N
InChI
InChI=1S/C22H28ClFO4/c1-11-6-13-14-8-16(24)15-7-12(26)4-5-21(15,3)22(14,23)18(28)9-20(13,2)19(11)17(27)10-25/h4-5,7,11,13-14,16,18-19,25,28H,6,8-10H2,1-3H3/t11-,13+,14+,16+,18+,19-,20+,21+,22+/m1/s1
IUPAC Name
(1R,2S,8S,10S,11S,13R,14S,15S,17S)-1-chloro-8-fluoro-17-hydroxy-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@H](C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(Cl)[C@@]2([H])C[C@H](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
  • 21-hydroxysteroid
  • Progestogin-skeleton
  • Pregnane-skeleton
  • 20-oxosteroid
  • 11-hydroxysteroid
  • 11-beta-hydroxysteroid
  • Oxosteroid
  • Halo-steroid
  • 6-halo-steroid
  • 9-halo-steroid
  • 3-oxosteroid
  • 3-oxo-delta-1,4-steroid
  • Delta-1,4-steroid
  • Cyclic alcohol
  • Alpha-hydroxy ketone
  • Cyclic ketone
  • Secondary alcohol
  • Ketone
  • Halohydrin
  • Chlorohydrin
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl fluoride
  • Alkyl chloride
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationFor short-term topical treatment of the inflammatory and pruritic manifestations of moderate to severe corticosteroid-responsive dermatoses of the scalp.
PharmacodynamicsLike other topical corticosteroids, clocortolone has anti-inflammatory, antipruritic, and vasoconstrictive properties. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Clocortolone is a moderate potency topical corticosteroid that should not be used with occlusive dressings. It is recommended that treatment should be limited to 2 consecutive weeks and therapy should be discontinued when adequate results have been achieved.
Mechanism of actionThe precise mechanism of the antiinflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. 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. These enzyme transcriptional changes are mediated by the drug binding first to the glucocorticoid receptor. This complex can migrate to the cell nucleus which then binds to DNA initiating genetic activation and repression of various genes.
AbsorptionTopical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Metabolized, primarily in the liver, and then excreted by the kidneys.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityTopically applied clocortolone can be absorbed in sufficient amounts to produce systemic effects. Symptoms of overdose include thinning of skin and suppression of adrenal cortex (decreased ability to respond to stress).
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+1.0
Blood Brain Barrier+0.9737
Caco-2 permeable+0.8054
P-glycoprotein substrateSubstrate0.7404
P-glycoprotein inhibitor INon-inhibitor0.7095
P-glycoprotein inhibitor IINon-inhibitor0.8814
Renal organic cation transporterNon-inhibitor0.8141
CYP450 2C9 substrateNon-substrate0.8412
CYP450 2D6 substrateNon-substrate0.8977
CYP450 3A4 substrateSubstrate0.7374
CYP450 1A2 substrateNon-inhibitor0.9164
CYP450 2C9 substrateNon-inhibitor0.9119
CYP450 2D6 substrateNon-inhibitor0.9061
CYP450 2C19 substrateNon-inhibitor0.9182
CYP450 3A4 substrateInhibitor0.6251
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.857
Ames testNon AMES toxic0.8537
CarcinogenicityNon-carcinogens0.8855
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9732 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9619
hERG inhibition (predictor II)Non-inhibitor0.5411
Pharmacoeconomics
Manufacturers
  • Dow pharmaceutical sciences inc
Packagers
Dosage forms
FormRouteStrength
Creamtopical.001 g/g
Prices
Unit descriptionCostUnit
Cloderm 0.1% Cream 45 gm Tube140.98USD tube
Cloderm 0.1% cream3.64USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.015 mg/mLALOGPS
logP2.73ALOGPS
logP2.47ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)13.53ChemAxon
pKa (Strongest Basic)-3.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity105.74 m3·mol-1ChemAxon
Polarizability41.8 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesD07AB21
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (167 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AldesleukinCorticosteroids such as clocortolone may diminish the antineoplastic effect of aldesleukin. Avoid conccurent use of corticosteroids with aldesleukin.
TelaprevirCorticosteroids such as clocortolone may decrease the serum concentration of telaprevir. Telaprevir may increase the serum concentration of Corticosteroids. Concurrent use of telaprevir and systemic corticosteroids is not recommended. When possible, consider alternatives, and if such a combination is necessary, use extra caution, monitoring patients for excessive systemic steroid effects as well as for diminished telaprevir effects.
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. Ali A, Balkovec JM, Greenlee M, Hammond ML, Rouen G, Taylor G, Einstein M, Ge L, Harris G, Kelly TM, Mazur P, Pandit S, Santoro J, Sitlani A, Wang C, Williamson J, Forrest MJ, Carballo-Jane E, Luell S, Lowitz K, Visco D: Discovery of betamethasone 17alpha-carbamates as dissociated glucocorticoid receptor modulators in the rat. Bioorg Med Chem. 2008 Aug 15;16(16):7535-42. Epub 2008 Jul 20. Pubmed
  2. Buchwald P: Glucocorticoid receptor binding: a biphasic dependence on molecular size as revealed by the bilinear LinBiExp model. Steroids. 2008 Feb;73(2):193-208. Epub 2007 Oct 11. Pubmed
  3. Tanigawa K, Nagase H, Ohmori K, Tanaka K, Miyake H, Kiniwa M, Ikizawa K: Species-specific differences in the glucocorticoid receptor transactivation function upon binding with betamethasone-esters. Int Immunopharmacol. 2002 Jun;2(7):941-50. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 27, 2013 16:30