Identification

Name
Clocortolone
Accession Number
DB00838  (APRD00877)
Type
Small Molecule
Groups
Approved
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
  • 9-chloro-6alpha-Fluoro-11beta,21-dihydroxy-16alpha-methyl-1,4-pregnadien-3,20-dione
  • 9-chloro-6alpha-Fluoro-16alpha-methyl-1,4-pregnadiene-11beta,21-diol-3,20-dione
  • Clocortolon
  • Clocortolona
  • Clocortolone
  • Clocortolonum
External IDs
SH 863
Product Ingredients
IngredientUNIICASInChI Key
Clocortolone pivalateQBL8IZH14X34097-16-0SXYZQZLHAIHKKY-GSTUPEFVSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ClodermCream0.001 g/1gTopicalCoria Laboratories1977-08-222016-05-01Us
ClodermCream0.001 g/1gTopicalPromius Pharma, LLC1977-08-22Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Clocortolone PivalateCream0.001 g/1gTopicalDr. Reddy's Laboratories Inc2014-02-17Not applicableUs
Categories
UNII
N8ZUB7XE0H
CAS number
4828-27-7
Weight
Average: 410.907
Monoisotopic: 410.166015296
Chemical Formula
C22H28ClFO4
InChI Key
YMTMADLUXIRMGX-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

Pharmacology

Indication

For short-term topical treatment of the inflammatory and pruritic manifestations of moderate to severe corticosteroid-responsive dermatoses of the scalp.

Associated Conditions
Pharmacodynamics

Like 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 action

The 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.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
Absorption

Topical 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 distribution
Not Available
Protein binding
Not Available
Metabolism

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

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Topically 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014976
KEGG Drug
D07719
PubChem Compound
5311052
PubChem Substance
46505290
ChemSpider
4470589
ChEBI
59582
Therapeutic Targets Database
DAP001190
PharmGKB
PA164744013
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Clocortolone
ATC Codes
D07AB21 — Clocortolone
FDA label
Download (167 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentPsoriasis1

Pharmacoeconomics

Manufacturers
  • Dow pharmaceutical sciences inc
Packagers
  • Coria Laboratories
  • DPT Laboratories Ltd.
  • Valeant Ltd.
Dosage forms
FormRouteStrength
CreamTopical0.001 g/1g
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.
Patents
Not Available

Properties

State
Solid
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.9119
CYP450 2D6 inhibitorNon-inhibitor0.9061
CYP450 2C19 inhibitorNon-inhibitor0.9182
CYP450 3A4 inhibitorInhibitor0.6251
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
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

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Hydroxysteroids
Direct Parent
21-hydroxysteroids
Alternative Parents
Gluco/mineralocorticoids, progestogins and derivatives / 20-oxosteroids / 11-beta-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Alpha-hydroxy ketones / Secondary alcohols / Chlorohydrins / Cyclic ketones
show 8 more
Substituents
21-hydroxysteroid / Progestogin-skeleton / 20-oxosteroid / Pregnane-skeleton / 6-halo-steroid / Halo-steroid / 3-oxo-delta-1,4-steroid / 9-halo-steroid / 3-oxosteroid / Oxosteroid
show 24 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
11beta-hydroxy steroid, glucocorticoid, 20-oxo steroid, fluorinated steroid, 3-oxo-Delta(1),Delta(4)-steroid, chlorinated steroid, 21-hydroxy steroid (CHEBI:59582)

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. 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. doi: 10.1016/j.bmc.2008.07.037. Epub 2008 Jul 20. [PubMed:18691892]
  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:18022656]
  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:12188035]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:50