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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:48:27
Primary Accession Number DB02300
Secondary Accession Number
  • EXPT02131
Name Calcipotriol
Drug Type
  • Approved
  • Nutraceutical
  • Small Molecule
Description Calcipotriol (INN) or calcipotriene (USAN) is a sythetic derivative of calcitriol or Vitamin D.
Synonyms
  1. Calcipotriene
Brand Names
  1. Davonex
  2. Dovonex
Brand Mixtures Not Available
Chemical IUPAC Name (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
Chemical Formula C27H40O3
Chemical Structure Structure
CAS Registry Number 112965-21-6
InChI Identifier InChI=1/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-
InChI Key LWQQLNNNIPYSNX-FJGALDFCBT
KEGG Drug D01125 Link Image
KEGG Compound Not Available
PubChem Compound 5282134 Link Image
PubChem Substance 7848188 Link Image
ChEBI ID Not Available
PharmGKB ID Not Available
HET ID MC9 Link Image
GenBank ID Not Available
Drug ID Number [DIN] 01976133 Link Image
RxList Link http://www.rxlist.com/cgi/generic/calcipo.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Calcipotriol Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 412.6047
Monoisotopic Molecular Weight 412.2977
State Solid
Melting Point Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 1.35e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity Not Available Source: PhysProp
Predicted LogP 4.63 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.49 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 1S19 Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES C[C@H](\C=C\[C@@H](O)C1CC1)[C@H]1CC[C@H]2[C@@]1(C)CCC\C2=C\C=C1\C[C@H](O)C[C@@H](O)C1=C
Canonical SMILES CC(C=CC(O)C1CC1)C1CCC2C1(C)CCCC2=CC=C1CC(O)CC(O)C1=C
Drug Category
  • Antipsoriatic Agents
  • Dermatologic Agents
  • Vitamin D3 Receptor inhibitor
ATC Codes Not Available
AHFS Codes Not Available
Indication For the treatment of moderate plaque psoriasis in adults.
Pharmacology 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.
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.
Protein Binding Not Available
Biotransformation 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.
Half Life Not Available
Dosage Forms
Form Route
Cream Topical
Ointment Topical
Shampoo Topical
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Not Available
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Vitamin D3 receptor
Drug Target 1 [top]
Target 1 ID 856
Target 1 Name Vitamin D3 receptor
Target 1 Synonyms
  1. 1,25-dihydroxyvitamin D3 receptor
  2. VDR
Target 1 Gene Name VDR
Target 1 Protein Sequence >Vitamin D3 receptor 
MEAMAASTSLPDPGDFDRNVPRICGVCGDRATGFHFNAMTCEGCKGFFRRSMKRKALFTC
PFNGDCRITKDNRRHCQACRLKRCVDIGMMKEFILTDEEVQRKREMILKRKEEEALKDSL
RPKLSEEQQRIIAILLDAHHKTYDPTYSDFCQFRPPVRVNDGGGSHPSRPNSRHTPSFSG
DSSSSCSDHCITSSDMMDSSSFSNLDLSEEDSDDPSVTLELSQLSMLPHLADLVSYSIQK
VIGFAKMIPGFRDLTSEDQIVLLKSSAIEVIMLRSNESFTMDDMSWTCGNQDYKYRVSDV
TKAGHSLELIEPLIKFQVGLKKLNLHEEEHVLLMAICIVSPDRPGVQDAALIEAIQDRLS
NTLQTYIRCRHPPPGSHLLYAKMIQKLADLRSLNEEHSKQYRCLSFQPECSMKLTPLVLE
VFGNEIS
Target 1 Number of Residues 434
Target 1 Molecular Weight 48290
Target 1 Theoretical pI 6.50
Target 1 GO Classification
Function
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 1 General Function Involved in transcription factor activity
Target 1 Specific Function Nuclear hormone receptor. VDR mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 340203 Link Image
Target 1 UniProtKB/Swiss-Prot ID P11473 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name VDR_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Nucleus
Target 1 Gene Sequence >1284 bp 
ATGGAGGCAATGGCGGCCAGCACTTCCCTGCCTGACCCTGGAGACTTTGACCGGAACGTG
CCCCGGATCTGTGGGGTGTGTGGAGACCGAGCCACTGGCTTTCACTTCAATGCTATGACC
TGTGAAGGCTGCAAAGGCTTCTTCAGGCGAAGCATGAAGCGGAAGGCACTATTCACCTGC
CCCTTCAACGGGGACTGCCGCATCACCAAGGACAACCGACGCCACTGCCAGGCCTGCCGG
CTCAAACGCTGTGTGGACATCGGCATGATGAAGGAGTTCATTCTGACAGATGAGGAAGTG
CAGAGGAAGCGGGAGATGATCCTGAAGCGGAAGGAGGAGGAGGCCTTGAAGGACAGTCTG
CGGCCCAAGCTGTCTGAGGAGCAGCAGCGCATCATTGCCATACTGCTGGACGCCCACCAT
AAGACCTACGACCCCACCTACTCCGACTTCTGCCAGTTCCGGCCTCCAGTTCGTGTGAAT
GATGGTGGAGGGAGCCATCCTTCCAGGCCCAACTCCAGACACACTCCCAGCTTCTCTGGG
GACTCCTCCTCCTCCTGCTCAGATCACTGTATCACCTCTTCAGACATGATGGACTCGTCC
AGCTTCTCCAATCTGGATCTGAGTGAAGAAGATTCAGATGACCCTTCTGTGACCCTAGAG
CTGTCCCAGCTCTCCATGCTGCCCCACCTGGCTGACCTGGTCAGTTACAGCATCCAAAAG
GTCATTGGCTTTGCTAAGATGATACCAGGATTCAGAGACCTCACCTCTGAGGACCAGATC
GTACTGCTGAAGTCAAGTGCCATTGAGGTCATCATGTTGCGCTCCAATGAGTCCTTCACC
ATGGACGACATGTCCTGGACCTGTGGCAACCAAGACTACAAGTACCGCGTCAGTGACGTG
ACCAAAGCCGGACACAGCCTGGAGCTGATTGAGCCCCTCATCAAGTTCCAGGTGGGACTG
AAGAAGCTGAACTTGCATGAGGAGGAGCATGTCCTGCTCATGGCCATCTGCATCGTCTCC
CCAGATCGTCCTGGGGTGCAGGACGCCGCGCTGATTGAGGCCATCCAGGACCGCCTGTCC
AACACACTGCAGACGTACATCCGCTGCCGCCACCCGCCCCCGGGCAGCCACCTGCTCTAT
GCCAAGATGATCCAGAAGCTAGCCGACCTGCGCAGCCTCAATGAGGAGCACTCCAAGCAG
TACCGCTGCCTCTCCTTCCAGCCTGAGTGCAGCATGAAGCTAACGCCCCTTGTGCTCGAA
GTGTTTGGCAATGAGATCTCCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID VDR Link Image
Target 1 GenAtlas ID VDR Link Image
Target 1 HGNC ID HGNC:12679 Link Image
Target 1 Chromosome Location 12
Target 1 Locus 12q13.11
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Rochel N, Wurtz JM, Mitschler A, Klaholz B, Moras D: The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol Cell. 2000 Jan;5(1):173-9. [PubMed Link Image]
  2. Mahajan MA, Samuels HH: A new family of nuclear receptor coregulators that integrate nuclear receptor signaling through CREB-binding protein. Mol Cell Biol. 2000 Jul;20(14):5048-63. [PubMed Link Image]
  3. Goto H, Chen KS, Prahl JM, DeLuca HF: A single receptor identical with that from intestine/T47D cells mediates the action of 1,25-dihydroxyvitamin D-3 in HL-60 cells. Biochim Biophys Acta. 1992 Aug 17;1132(1):103-8. [PubMed Link Image]
  4. Saijo T, Ito M, Takeda E, Huq AH, Naito E, Yokota I, Sone T, Pike JW, Kuroda Y: A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection. Am J Hum Genet. 1991 Sep;49(3):668-73. [PubMed Link Image]
  5. Yu XP, Mocharla H, Hustmyer FG, Manolagas SC: Vitamin D receptor expression in human lymphocytes. Signal requirements and characterization by western blots and DNA sequencing. J Biol Chem. 1991 Apr 25;266(12):7588-95. [PubMed Link Image]
  6. Sone T, Marx SJ, Liberman UA, Pike JW: A unique point mutation in the human vitamin D receptor chromosomal gene confers hereditary resistance to 1,25-dihydroxyvitamin D3. Mol Endocrinol. 1990 Apr;4(4):623-31. [PubMed Link Image]
  7. Baker AR, McDonnell DP, Hughes M, Crisp TM, Mangelsdorf DJ, Haussler MR, Pike JW, Shine J, O'Malley BW: Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci U S A. 1988 May;85(10):3294-8. [PubMed Link Image]
  8. Hughes MR, Malloy PJ, Kieback DG, Kesterson RA, Pike JW, Feldman D, O'Malley BW: Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets. Science. 1988 Dec 23;242(4886):1702-5. [PubMed Link Image]
  9. Rut AR, Hewison M, Kristjansson K, Luisi B, Hughes MR, O'Riordan JL: Two mutations causing vitamin D resistant rickets: modelling on the basis of steroid hormone receptor DNA-binding domain crystal structures. Clin Endocrinol (Oxf). 1994 Nov;41(5):581-90. [PubMed Link Image]
  10. Malloy PJ, Weisman Y, Feldman D: Hereditary 1 alpha,25-dihydroxyvitamin D-resistant rickets resulting from a mutation in the vitamin D receptor deoxyribonucleic acid-binding domain. J Clin Endocrinol Metab. 1994 Feb;78(2):313-6. [PubMed Link Image]
  11. 8381803 Yagi H, Ozono K, Miyake H, Nagashima K, Kuroume T, Pike JW: A new point mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor in a kindred with hereditary 1,25-dihydroxyvitamin D-resistant rickets. J Clin Endocrinol Metab. 1993 Feb;76(2):509-12.
  12. 8392085 Kristjansson K, Rut AR, Hewison M, O'Riordan JL, Hughes MR: Two mutations in the hormone binding domain of the vitamin D receptor cause tissue resistance to 1,25 dihydroxyvitamin D3. J Clin Invest. 1993 Jul;92(1):12-6.
  13. 8675579 Lin NU, Malloy PJ, Sakati N, al-Ashwal A, Feldman D: A novel mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor causes hereditary 1,25-dihydroxyvitamin D-resistant rickets. J Clin Endocrinol Metab. 1996 Jul;81(7):2564-9.
  14. 8961271 Whitfield GK, Selznick SH, Haussler CA, Hsieh JC, Galligan MA, Jurutka PW, Thompson PD, Lee SM, Zerwekh JE, Haussler MR: Vitamin D receptors from patients with resistance to 1,25-dihydroxyvitamin D3: point mutations confer reduced transactivation in response to ligand and impaired interaction with the retinoid X receptor heterodimeric partner. Mol Endocrinol. 1996 Dec;10(12):1617-31.
  15. 9005998 Malloy PJ, Eccleshall TR, Gross C, Van Maldergem L, Bouillon R, Feldman D: Hereditary vitamin D resistant rickets caused by a novel mutation in the vitamin D receptor that results in decreased affinity for hormone and cellular hyporesponsiveness. J Clin Invest. 1997 Jan 15;99(2):297-304.
  16. 9212063 Miyamoto K, Kesterson RA, Yamamoto H, Taketani Y, Nishiwaki E, Tatsumi S, Inoue Y, Morita K, Takeda E, Pike JW: Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol. 1997 Jul;11(8):1165-79.
  17. 9267036 Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM: Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569-80.
Target 1 Drug References
  1. 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 Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

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.