DrugBank: Clocortolone (DB00838)

targets (1)

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Clocortolone pivalate

Salts

Not Available

Brand names

Name	Company
Cloderm

Brand mixtures

Not Available

Categories

Corticosteroids, topical

CAS number

34097-16-0

Weight

Average: 410.907
Monoisotopic: 410.166015296

Chemical Formula

C₂₂H₂₈ClFO₄

InChI Key

InChIKey=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

Plain Text

IUPAC Name

(1R,2S,8S,10S,11S,13R,14S,15S,17S)-1-chloro-8-fluoro-17-hydroxy-14-(2-hydroxyacetyl)-2,13,15-trimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

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

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.

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

Pharmacoeconomics

Manufacturers

Dow pharmaceutical sciences inc

Packagers

Dosage forms

Form	Route	Strength
Cream	Topical

Prices

Unit description	Cost	Unit
Cloderm 0.1% Cream 45 gm Tube	140.98 USD	tube
Cloderm 0.1% cream	3.64 USD	g

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

solid

Experimental Properties

Property	Value	Source
logP	3.8	Not Available

Predicted Properties

Property	Value	Source
water solubility	1.50e-02 g/l	ALOGPS
logP	2.73	ALOGPS
logP	2.47	ChemAxon
logS	-4.4	ALOGPS
pKa (strongest acidic)	13.53	ChemAxon
pKa (strongest basic)	-3.3	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	4	ChemAxon
hydrogen donor count	2	ChemAxon
polar surface area	74.6	ChemAxon
rotatable bond count	2	ChemAxon
refractivity	105.74	ChemAxon
polarizability	41.8	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D02287
ChEBI	59582
ChEMBL	59582
Therapeutic Targets Database	DAP001190
PharmGKB	PA164744013
RxList	http://www.rxlist.com/cgi/generic2/clocortolone.htm
Drugs.com	http://www.drugs.com/cdi/clocortolone.html
Wikipedia	http://en.wikipedia.org/wiki/Clocortolone

ATC Codes

D07AB21

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

show (167 KB)

MSDS

Not Available

Interactions

Drug Interactions

Drug

Interaction

Aldesleukin

Corticosteroids such as clocortolone may diminish the antineoplastic effect of aldesleukin. Avoid conccurent use of corticosteroids with aldesleukin.

Telaprevir

Corticosteroids 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 Interactions

Not Available

Targets
1. Glucocorticoid receptor Pharmacological action: yes Actions: agonist Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) 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 growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth Organism class: human UniProt ID: P04150 Gene: NR3C1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 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 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

Targets

1. Glucocorticoid receptor

Pharmacological action: yes
Actions: agonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) 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 growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth

Organism class: human
UniProt ID: P04150 Link_out

Gene: NR3C1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
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
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

Comments

Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19