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Identification
NameCalcipotriol
Accession NumberDB02300  (EXPT02131)
Typesmall molecule
Groupsapproved
Description

Calcipotriol (INN) or calcipotriene (USAN) is a sythetic derivative of calcitriol or Vitamin D.

Structure
Thumb
Synonyms
SynonymLanguageCode
CalcipotrieneNot AvailableUSAN
SaltsNot Available
Brand names
NameCompany
CalcitreneNot Available
DaivonexNot Available
DovonexNot Available
SORILUXNot Available
Brand mixtures
Brand NameIngredients
TACLONEXBetamethasone + Calcipotriol
TaclonexBetamethasone + Calcipotriol
Categories
CAS number112965-21-6
WeightAverage: 412.6047
Monoisotopic: 412.297745146
Chemical FormulaC27H40O3
InChI KeyLWQQLNNNIPYSNX-UROSTWAQSA-N
InChI
InChI=1S/C27H40O3/c1-17(6-13-25(29)20-8-9-20)23-11-12-24-19(5-4-14-27(23,24)3)7-10-21-15-22(28)16-26(30)18(21)2/h6-7,10,13,17,20,22-26,28-30H,2,4-5,8-9,11-12,14-16H2,1,3H3/b13-6+,19-7+,21-10-/t17-,22-,23-,24+,25-,26+,27-/m1/s1
IUPAC Name
(1R,3S,5Z)-5-{2-[(1R,3aS,4E,7aR)-1-[(2R,3E,5S)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol
SMILES
O[C@H](\C=C\[C@@H](C)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C)C1CC1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassVitamin D and Derivatives
Direct parentVitamin D and Derivatives
Alternative parentsSesterterpenes; Cyclohexanols; Cyclic Alcohols and Derivatives; Polyamines
Substituentscyclohexanol; cyclic alcohol; secondary alcohol; polyamine; alcohol
Classification descriptionThis compound belongs to the vitamin d and derivatives. These are compounds containing a secosteroid backbone, usually secoergostane or secocholestane.
Pharmacology
IndicationFor the treatment of moderate plaque psoriasis in adults.
PharmacodynamicsCalcipotriene is a synthetic analog of vitamin D. In humans, the natural supply of vitamin D depends mainly on exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol to vitamin D3 (cholecalciferol) in the skin.
Mechanism of actionThe precise mechanism of calcipotriol in remitting psoriasis is not well-understood. However, it has been shown to have comparable affinity with calcitriol for the Vitamin D receptor, while being less than 1% as active as the calcitriol in regulating calcium metabolism. The Vitamin D receptor (VDR) belongs to the steroid/thyroid receptor superfamily, and is found on the cells of many different tissues including the thyroid, bone, kindney, and T cells of the immune system. T cells are known to play a role in psoriasis, and it is thought that the binding of calcipotriol to the VDR modulates the T cells gene transcription of cell differentiation and proliferation related genes.
AbsorptionClinical studies with radiolabeled ointment indicate that approximately 6% (+3%, SD) of the applied dose of calcipotriene is absorbed systemically when the ointment is applied topically to psoriasis plaques or 5% (+2.6%, SO) when applied to normal skin.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic. Calcipotriene metabolism following systemic uptake is rapid, and occurs via a similar pathway to the natural hormone. The primary metabolites are much less potent than the parent compound.

Route of eliminationThe active form of the vitamin, 1,25-dihydroxy vitamin D3 (calcitriol), is known to be recycled via the liver and excreted in the bile. There is evidence that maternal 1,25-dihydroxy vitamin D3 (calcitriol) may enter the fetal circulation, but it is not known whether it is excreted in human milk.
Half lifeNot Available
ClearanceNot Available
ToxicityTopically applied calcipotriene can be absorbed in sufficient amounts to produce systemic effects. Elevated serum calcium has been observed with excessive use of calcipotriene.
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 + 0.9945
Blood Brain Barrier + 0.8426
Caco-2 permeable + 0.7643
P-glycoprotein substrate Substrate 0.7718
P-glycoprotein inhibitor I Non-inhibitor 0.7297
P-glycoprotein inhibitor II Non-inhibitor 0.9687
Renal organic cation transporter Non-inhibitor 0.813
CYP450 2C9 substrate Non-substrate 0.8383
CYP450 2D6 substrate Non-substrate 0.8975
CYP450 3A4 substrate Substrate 0.7113
CYP450 1A2 substrate Non-inhibitor 0.7455
CYP450 2C9 substrate Non-inhibitor 0.7898
CYP450 2D6 substrate Non-inhibitor 0.9336
CYP450 2C19 substrate Non-inhibitor 0.7994
CYP450 3A4 substrate Non-inhibitor 0.8014
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7475
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.9332
Biodegradation Not ready biodegradable 0.9871
Rat acute toxicity 3.9699 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9198
hERG inhibition (predictor II) Non-inhibitor 0.8018
Pharmacoeconomics
Manufacturers
  • Leo pharmaceutical products ltd
  • Glenmark generics inc usa
  • Hi tech pharmacal co inc
  • Nycomed us inc
  • Tolmar inc
Packagers
Dosage forms
FormRouteStrength
CreamTopical
OintmentTopical
ShampooTopical
Prices
Unit descriptionCostUnit
Dovonex 0.005% Cream 120 gm Tube607.03USDtube
Dovonex 0.005% Solution 60ml Bottle323.98USDbottle
Dovonex 0.005% Cream 60 gm Tube303.51USDtube
Dovonex 0.005% cream4.23USDg
Dovonex 50 mcg/ml Solution0.84USDml
Dovonex 50 mcg/g Cream0.83USDg
Dovonex 50 mcg/g Ointment0.81USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States57634261995-06-092015-06-09
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility1.35e-02 g/lALOGPS
logP4.63ALOGPS
logP3.84ChemAxon
logS-4.5ALOGPS
pKa (strongest acidic)14.39ChemAxon
pKa (strongest basic)-1.6ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count3ChemAxon
polar surface area60.69ChemAxon
rotatable bond count5ChemAxon
refractivity125.45ChemAxon
polarizability49.59ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Andrzej Kutner, Michal Chodynski, Teresa Ryznar, Hanna Fitak, Jerzy Winiarski, Bartlomiej Gorecki, Agnieszka Burzynska, Wieslaw Szelejewski, “Process for Preparation of Pharmaceutically Pure Anhydrous Calcipotriol.” U.S. Patent US20080214876, issued September 04, 2008.

US20080214876
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD01125
ChEBI50749
ChEMBLCHEMBL1234231
Therapeutic Targets DatabaseDAP000292
PharmGKBPA448714
IUPHAR2778
Guide to Pharmacology2778
HETMC9
Drug Product Database1976133
RxListhttp://www.rxlist.com/cgi/generic/calcipo.htm
WikipediaCalcipotriol
ATC CodesD05AX02
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AlfacalcidolVitamin D Analogs may enhance the adverse/toxic effect of other Vitamin D Analogs. Avoid combined use of multiple vitamin D analogs (at pharmacologic doses). Prescribing information for calcitriol, doxercalciferol, paricalcitol, and alfacalcidol each specifically cautions against such combined use.
Aluminum hydroxideVitamin D Analogs may increase the serum concentration of Aluminum Hydroxide. Specifically, the absorption of aluminum may be increased, leading to increased serum aluminum concentrations. Avoid chronic and/or excessive use of aluminum and aluminum-containing products in patients who are also taking vitamin D analogs. Any patients consuming such a combination should be monitored closely for aluminum status and signs/symptoms of aluminum-related toxicities.
CholecalciferolVitamin D Analogs may enhance the adverse/toxic effect of other Vitamin D Analogs. Avoid combined use of multiple vitamin D analogs (at pharmacologic doses). hough not specified in the prescribing information for calcipotriene, cholecalciferol, and ergocalciferol, each contains warnings regarding the potential for vitamin D toxicity.
OrlistatOrlistat may decrease the serum concentration of fat soluble vitamins like vitamin D. Hence, this applies to calcipotriol, a synthetic derivative of vitamin D. Administer oral fat soluble vitamins at least 2 hours before or after the administration of orlistat. Avoid concomitant administration due to the risk of impaired vitamin absorption. Similar precautions do not apply to parenterally administered fat soluble vitamins.
SucralfateVitamin D Analogs may increase the serum concentration of Sucralfate. Specifically, the absorption of aluminum from sucralfate may be increased, leading to an increase in the serum aluminum concentration. Avoid chronic and/or excessive use of aluminum and aluminum-containing products (such as sucralfate) in patients who are also taking vitamin D analogs. Any patients consuming such a combination should be monitored closely for aluminum status and signs/symptoms of aluminum-related toxicities.
Food InteractionsNot Available

Targets

1. Vitamin D3 receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Vitamin D3 receptor P11473 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

Enzymes

1. Myeloperoxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Myeloperoxidase P05164 Details

References:

  1. Sato H, Ogino Y, Takagi H, Hata J, Asano S, Ohta T, Komoriya K: Pharmacological profiles of high-concentration (20 microg/g) tacalcitol ointment: effects on cutaneous inflammation, epidermal proliferation, and differentiation in mice. J Dermatol. 2003 Jul;30(7):510-24. Pubmed

2. 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial Q07973 Details

References:

  1. Jones G, Byford V, West S, Masuda S, Ibrahim G, Kaufmann M, Knutson JC, Strugnell S, Mehta R: Hepatic activation and inactivation of clinically-relevant vitamin D analogs and prodrugs. Anticancer Res. 2006 Jul-Aug;26(4A):2589-95. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 04, 2013 11:10