DrugBank: Calcipotriol (DB02300)

targets (1)

Identification

Name

Calcipotriol

Accession Number

DB02300 (EXPT02131)

Type

small molecule

Groups

approved, nutraceutical

Description

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

Structure

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

Synonyms

Calcipotriene

Brand names

Davonex
Dovonex

Brand name mixtures

Not Available

Categories

Dermatologic Agents
Vitamin D3 Receptor inhibitor
Antipsoriatic Agents

CAS number

112965-21-6

Weight

Average: 412.6047
Monoisotopic: 412.297745146

Chemical Formula

C₂₇H₄₀O₃

InChI Key

InChIKey=LWQQLNNNIPYSNX-FJGALDFCSA-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-

Plain Text

IUPAC Name

(5Z)-5-{2-[(4Z)-1-[(3E)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol

SMILES

CC(\C=C\C(O)C1CC1)C1CCC2\C(CCCC12C)=C/C=C1/CC(O)CC(O)C1=C

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Steroids and Steroid Derivatives

Substructures

Steroids and Steroid Derivatives
Hydroxy Compounds
Alkanes and Alkenes
Cyclopropane and Derivatives
Isoprenes
Alcohols and Polyols

Pharmacology

Indication

For the treatment of moderate plaque psoriasis in adults.

Pharmacodynamics

Calcipotriene 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 action

The 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.

Absorption

Clinical 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 distribution

Not Available

Protein binding

Not 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 elimination

The 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 life

Not Available

Clearance

Not Available

Toxicity

Topically 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

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Leo pharmaceutical products ltd
Glenmark generics inc usa
Hi tech pharmacal co inc
Nycomed us inc
Tolmar inc

Packagers

Dosage forms

Form	Route	Strength
Cream	Topical
Ointment	Topical
Shampoo	Topical

Prices

Unit description	Cost	Unit
Dovonex 0.005% Cream 120 gm Tube	607.03 USD	tube
Dovonex 0.005% Solution 60ml Bottle	323.98 USD	bottle
Dovonex 0.005% Cream 60 gm Tube	303.51 USD	tube
Dovonex 0.005% cream	4.23 USD	g
Dovonex 50 mcg/ml Solution	0.84 USD	ml
Dovonex 50 mcg/g Cream	0.83 USD	g
Dovonex 50 mcg/g Ointment	0.81 USD	g

Patents

Country	Patent Number	Approved	Expires
United States	5763426	1995-06-09	2015-06-09

Properties

State

solid

Melting point

Not Available

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
water solubility	1.35e-02 g/l	ALOGPS
logP	4.63	ALOGPS
logP	3.84	ChemAxon Molconvert
logS	-4.49	ALOGPS
pKa	15.29	ChemAxon Molconvert
hydrogen acceptor count	3	ChemAxon Molconvert
hydrogen donor count	3	ChemAxon Molconvert
polar surface area	60.69	ChemAxon Molconvert
rotatable bond count	5	ChemAxon Molconvert
refractivity	125.45	ChemAxon Molconvert
polarizability	49.26	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D01125
PubChem Compound	6376277
PubChem Substance	46507122
ChEBI	50749
ChEMBL	50749
Therapeutic Targets Database	DAP000292
HET	MC9
Drug Product Database	1976133
RxList	http://www.rxlist.com/cgi/generic/calcipo.htm
Wikipedia	http://en.wikipedia.org/wiki/Calcipotriol

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

1S19

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Vitamin D3 receptor Pharmacological action: unknown Actions: antagonist Nuclear hormone receptor. VDR mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes Organism class: human UniProt ID: P11473 Gene: VDR Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Targets

1. Vitamin D3 receptor

Pharmacological action: unknown
Actions: antagonist

Nuclear hormone receptor. VDR mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes

Organism class: human
UniProt ID: P11473 Link_out

Gene: VDR

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

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:11

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.