Clocortolone
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
Structure for Clocortolone (DB00838)
- 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
Ingredient UNII CAS InChI Key Clocortolone pivalate QBL8IZH14X 34097-16-0 SXYZQZLHAIHKKY-GSTUPEFVSA-N - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Cloderm Cream 0.001 g/1g Topical Coria Laboratories 1977-08-22 2016-05-01 US 
Cloderm Cream 0.001 g/1g Topical Promius Pharma, LLC 1977-08-22 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Clocortolone Pivalate Cream 0.001 g/1g Topical Dr. Reddy's Laboratories Inc 2014-02-17 Not applicable US - Categories
- Adrenal Cortex Hormones
- Anti-Inflammatory Agents
- Corticosteroid Hormone Receptor Agonists
- Corticosteroids
- Corticosteroids, Dermatological Preparations
- Corticosteroids, Moderately Potent (Group II)
- Dermatologicals
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Immunosuppressive Agents
- Pregnadienediols
- Pregnadienes
- Pregnanes
- Steroids
- Steroids, Fluorinated
- 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.
Target Actions Organism AGlucocorticoid receptor agonistHuman - 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
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
Pharmacoeconomics
- Manufacturers
- Dow pharmaceutical sciences inc
- Packagers
- Coria Laboratories
- DPT Laboratories Ltd.
- Valeant Ltd.
- Dosage forms
Form Route Strength Cream Topical 0.001 g/1g - Prices
Unit description Cost Unit Cloderm 0.1% Cream 45 gm Tube 140.98USD tube Cloderm 0.1% cream 3.64USD g DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 3.8 Not Available - Predicted Properties
Property Value Source Water Solubility 0.015 mg/mL 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 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 105.74 m3·mol-1 ChemAxon Polarizability 41.8 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9737 Caco-2 permeable + 0.8054 P-glycoprotein substrate Substrate 0.7404 P-glycoprotein inhibitor I Non-inhibitor 0.7095 P-glycoprotein inhibitor II Non-inhibitor 0.8814 Renal organic cation transporter Non-inhibitor 0.8141 CYP450 2C9 substrate Non-substrate 0.8412 CYP450 2D6 substrate Non-substrate 0.8977 CYP450 3A4 substrate Substrate 0.7374 CYP450 1A2 substrate Non-inhibitor 0.9164 CYP450 2C9 inhibitor Non-inhibitor 0.9119 CYP450 2D6 inhibitor Non-inhibitor 0.9061 CYP450 2C19 inhibitor Non-inhibitor 0.9182 CYP450 3A4 inhibitor Inhibitor 0.6251 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.857 Ames test Non AMES toxic 0.8537 Carcinogenicity Non-carcinogens 0.8855 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.9732 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9619 hERG inhibition (predictor II) Non-inhibitor 0.5411
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not 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
- 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]
- 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]
- 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 October 01, 2018 16:37