Calcipotriol (T3D3062)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2009-07-21 20:28:57 UTC
Update Date2014-12-24 20:25:56 UTC
Accession NumberT3D3062
Identification
Common NameCalcipotriol
ClassSmall Molecule
DescriptionCalcipotriol is only found in individuals that have used or taken this drug. It is a synthetic derivative of calcitriol or Vitamin D.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.
Compound Type
  • Antipsoriatic Agent
  • Dermatologic Agent
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
  • Vitamin D3 Receptor inhibitor
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
Calcipotriene
Calcitrene
Daivonex
Dovonex
SORILUX
Chemical FormulaC27H40O3
Average Molecular Mass412.605 g/mol
Monoisotopic Mass412.298 g/mol
CAS Registry Number112965-21-6
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
Traditional Namecalcipotriol
SMILES[H]\C(\C(\[H])=C1/CCC[C@@]2(C)[C@@]1([H])CC[C@]2([H])[C@]([H])(C)C(\[H])=C(/[H])[C@@]([H])(O)C1CC1)=C1/C[C@@]([H])(O)C[C@]([H])(O)C1=C
InChI IdentifierInChI=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
InChI KeyInChIKey=LWQQLNNNIPYSNX-UROSTWAQSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as vitamin d and derivatives. Vitamin D and derivatives are compounds containing a secosteroid backbone, usually secoergostane or secocholestane.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassVitamin D and derivatives
Direct ParentVitamin D and derivatives
Alternative Parents
Substituents
  • Triterpenoid
  • Cyclic alcohol
  • Secondary alcohol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility1.35e-02 g/L
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.014 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 Area60.69 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity125.45 m³·mol⁻¹ChemAxon
Polarizability49.59 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00kg-2019000000-25fe74385dfaaadc4f642017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-03di-2200159000-60ddca8d21526e4244de2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-002b-0019100000-dd8b67e911e2c011a4512016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00fr-3349000000-721114fcaf3ed169df5d2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fki-9568000000-c7e61ad61191fce88abe2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0006900000-01ce5bd91cb0ca4dcbec2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01ox-2009300000-7f4afaeab87ae0e61d8d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9005000000-075615c00f3c0728d5ed2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-06tb-0139300000-4a9257a0b1cf140f5b7a2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0cki-1269200000-926c7873d1b6b3d9d1442021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000b-2494000000-3044d26933d8919ecbfb2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0002900000-6b048e3e028e205ac5982021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-1505900000-d9fa5fd00776cc0e0e282021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-0101900000-12080aba78c8a692b2ab2021-10-11View Spectrum
Toxicity Profile
Route of ExposureClinical 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.
Mechanism of ToxicityThe 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.
MetabolismHepatic. 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.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of moderate plaque psoriasis in adults.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsTopically applied calcipotriene can be absorbed in sufficient amounts to produce systemic effects. Elevated serum calcium has been observed with excessive use of calcipotriene.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB02300
HMDB IDHMDB15567
PubChem Compound ID5288783
ChEMBL IDCHEMBL1234231
ChemSpider ID4450880
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID50749
BioCyc IDNot Available
CTD IDNot Available
Stitch IDCalcipotriol
PDB IDMC9
ACToR IDNot Available
Wikipedia LinkCalcipotriol
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.

MSDST3D3062.pdf
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

Target Details
1. Vitamin D3 receptor
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.
Gene Name:
VDR
Uniprot ID:
P11473
Molecular Weight:
48288.64 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation0.00031 uMNot AvailableBindingDB 50369964
References
  1. Thacher SM, Vasudevan J, Tsang KY, Nagpal S, Chandraratna RA: New dermatological agents for the treatment of psoriasis. J Med Chem. 2001 Feb 1;44(3):281-97. [11462969 ]