You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2009-07-21 20:26:12 UTC
Update Date2014-12-24 20:25:49 UTC
Accession NumberT3D2703
Identification
Common NameCholecalciferol
ClassSmall Molecule
DescriptionCholecalciferol is only found in individuals that have used or taken this drug. It is a derivative of 7-dehydroxycholesterol formed by ultraviolet rays breaking of the C9-C10 bond. It differs from ergocalciferol in having a single bond between C22 and C23 and lacking a methyl group at C24. [PubChem]The first step involved in the activation of vitamin D3 is a 25-hydroxylation which is catalysed by the 25-hydroxylase in the liver and then by other enzymes. The mitochondrial sterol 27-hydroxylase catalyses the first reaction in the oxidation of the side chain of sterol intermediates. The active form of vitamin D3 (calcitriol) binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.
Compound Type
  • Antihypocalcemic Agent
  • Antihypoparathyroid Agent
  • Antithyroid Agent
  • Bone Density Conservation Agent
  • Drug
  • Essential Vitamin
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Nutraceutical
  • Organic Compound
  • Synthetic Compound
  • Vitamin
  • Vitamin D
Chemical Structure
Thumb
Synonyms
Synonym
(+)-vitamin D3
(1S,3Z)-3-[(2e)-2-[(1R,3AR,7as)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexan-1-ol
(3beta,5Z,7e)-9,10-Secocholesta-5,7,10(19)-trien-3-ol
(5Z,7e)-(3S)-9,10-Secocholesta-5,7,10(19)-trien-3-ol
Activated 7-dehydrocholesterol
Calciol
CC
Colecalciferol
delta-D
Micro-D
Oleovitamin D3
Optimal-D
Vigantol
Vitamin D3
Chemical FormulaC27H44O
Average Molecular Mass384.638 g/mol
Monoisotopic Mass384.339 g/mol
CAS Registry Number67-97-0
IUPAC Name(1S,3Z)-3-{2-[(1R,3aS,4E,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexan-1-ol
Traditional Namevitamin D3
SMILES[H]\C(\C(\[H])=C1/CCC[C@@]2(C)[C@@]1([H])CC[C@]2([H])[C@]([H])(C)CCCC(C)C)=C1/C[C@@]([H])(O)CCC1=C
InChI IdentifierInChI=1S/C27H44O/c1-19(2)8-6-9-21(4)25-15-16-26-22(10-7-17-27(25,26)5)12-13-23-18-24(28)14-11-20(23)3/h12-13,19,21,24-26,28H,3,6-11,14-18H2,1-2,4-5H3/b22-12+,23-13-/t21-,24+,25-,26+,27-/m1/s1
InChI KeyInChIKey=QYSXJUFSXHHAJI-YRZJJWOYSA-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
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point84.5°C
Boiling Point496.4°C
SolubilityInsoluble
LogP7.5
Predicted Properties
PropertyValueSource
Water Solubility0.00038 g/LALOGPS
logP7.98ALOGPS
logP7.13ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)18.38ChemAxon
pKa (Strongest Basic)-1.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity123.22 m³·mol⁻¹ChemAxon
Polarizability49.63 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0aou-3029000000-1950c74de34369a70400JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-002f-9207800000-c6f808a014153de38d58JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014r-0129000000-80de8aabbfb587d8f7b9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0abi-2595000000-1f5db35cc732efef5e27JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pb9-7195000000-b742ddd81b2f98395fabJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0009000000-70f22151bd69b3307086JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-0009000000-7ff3c3cf4e98856a166bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-1249000000-8756607b9fd7d6008ac9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0459000000-cdb5561f3458bde4c2f1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0kmj-7494000000-5a36ac0547956f9ac058JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-3930000000-c62b5a8a92e3487b90edJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0009000000-bfd82bd18d8804cfa1d2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-0009000000-d168cadb843f05c02d05JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-0539000000-277213cec95d0ba155c5JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureOral, readily absorbed
Mechanism of ToxicityThe first step involved in the activation of vitamin D3 is a 25-hydroxylation which is catalysed by the 25-hydroxylase in the liver and then by other enzymes. The mitochondrial sterol 27-hydroxylase catalyses the first reaction in the oxidation of the side chain of sterol intermediates. The active form of vitamin D3 (calcitriol) binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.
MetabolismWithin the liver, cholecalciferal is hydroxylated to calcidiol (25-hydroxycholecalciferol) by the enzyme 25-hydroxylase. Within the kidney, calcidiol serves as a substrate for 1-alpha-hydroxylase, yielding calcitriol (1,25-dihydroxycholecalciferol), the biologically active form of vitamin D3. Half Life: Several weeks
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of vitamin D deficiency or insufficiency, refractory rickets (vitamin D resistant rickets), familial hypophosphatemia and hypoparathyroidism, and in the management of hypocalcemia and renal osteodystrophy in patients with chronic renal failure undergoing dialysis. Also used in conjunction with calcium in the management and prevention of primary or corticosteroid-induced osteoporosis.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsHypercalcemia - Early symptoms of hypercalcemia, include nausea and vomiting, weakness, headache, somnolence, dry mouth, constipation, metallic taste, muscle pain and bone pain. Late symptoms and signs of hypercalcemia, include polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis, pancreatitis, photophobia, rhinorrhea, pruritis, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated ALT (SGPT) and AST (SGOT), ectopic calcification, nephrocalcinosis, hypertension and cardiac arrhythmias.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00169
HMDB IDHMDB14315
PubChem Compound ID5280795
ChEMBL IDCHEMBL1042
ChemSpider ID4444353
KEGG IDC05443
UniProt IDNot Available
OMIM ID270400
ChEBI ID28940
BioCyc IDVITAMIN_D_%7B3%7D
CTD IDNot Available
Stitch IDCholecalciferol
PDB IDNot Available
ACToR ID7582
Wikipedia LinkCholecalciferol
References
Synthesis Reference

Jean Jolly, Primo Rizzi, Jean Taillardat, “1.alpha.,25.alpha.-Dihydroxy-cholecalciferol and methods for the production thereof.” U.S. Patent US4435325, issued May, 1977.

MSDSLink
General References
  1. Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. [15531486 ]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Catalyzes the first step in the oxidation of the side chain of sterol intermediates; the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol. Has also a vitamin D3-25-hydroxylase activity.
Gene Name:
CYP27A1
Uniprot ID:
Q02318
Molecular Weight:
60234.28 Da
References
  1. Lehmann B, Tiebel O, Meurer M: Expression of vitamin D3 25-hydroxylase (CYP27) mRNA after induction by vitamin D3 or UVB radiation in keratinocytes of human skin equivalents--a preliminary study. Arch Dermatol Res. 1999 Sep;291(9):507-10. [10541881 ]
  2. Sawada N, Sakaki T, Yoneda S, Kusudo T, Shinkyo R, Ohta M, Inouye K: Conversion of vitamin D3 to 1alpha,25-dihydroxyvitamin D3 by Streptomyces griseolus cytochrome P450SU-1. Biochem Biophys Res Commun. 2004 Jul 16;320(1):156-64. [15207715 ]
  3. Uchida E, Kagawa N, Sakaki T, Urushino N, Sawada N, Kamakura M, Ohta M, Kato S, Inouye K: Purification and characterization of mouse CYP27B1 overproduced by an Escherichia coli system coexpressing molecular chaperonins GroEL/ES. Biochem Biophys Res Commun. 2004 Oct 15;323(2):505-11. [15369780 ]
  4. Sakaki T, Kagawa N, Yamamoto K, Inouye K: Metabolism of vitamin D3 by cytochromes P450. Front Biosci. 2005 Jan 1;10:119-34. Print 2005 Jan 1. [15574355 ]
  5. Tokar EJ, Webber MM: Cholecalciferol (vitamin D3) inhibits growth and invasion by up-regulating nuclear receptors and 25-hydroxylase (CYP27A1) in human prostate cancer cells. Clin Exp Metastasis. 2005;22(3):275-84. [16158255 ]
General Function:
Vitamin transporter activity
Specific Function:
Involved in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5 alpha for neutrophils in inflammation and macrophage activation.
Gene Name:
GC
Uniprot ID:
P02774
Molecular Weight:
52963.025 Da
References
  1. Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, Melsen F, Christensen EI, Willnow TE: An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999 Feb 19;96(4):507-15. [10052453 ]
  2. Verboven C, Rabijns A, De Maeyer M, Van Baelen H, Bouillon R, De Ranter C: A structural basis for the unique binding features of the human vitamin D-binding protein. Nat Struct Biol. 2002 Feb;9(2):131-6. [11799400 ]
  3. Houghton LA, Vieth R: The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006 Oct;84(4):694-7. [17023693 ]
  4. Yamamoto N, Naraparaju VR: Vitamin D3-binding protein as a precursor for macrophage activating factor in the inflammation-primed macrophage activation cascade in rats. Cell Immunol. 1996 Jun 15;170(2):161-7. [8660814 ]
  5. Yamamoto N, Naraparaju VR: Role of vitamin D3-binding protein in activation of mouse macrophages. J Immunol. 1996 Aug 15;157(4):1744-9. [8759764 ]
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
References
  1. Reinhart GA: Vitamin D analogs: novel therapeutic agents for cardiovascular disease? Curr Opin Investig Drugs. 2004 Sep;5(9):947-51. [15503649 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  3. Fujishima T, Tsuji G, Tanaka C, Harayama H: Novel vitamin D receptor ligands having a carboxyl group as an anchor to arginine 274 in the ligand-binding domain. J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):60-2. doi: 10.1016/j.jsbmb.2010.04.020. Epub 2010 May 6. [20435140 ]
  4. Eloranta JJ, Hiller C, Juttner M, Kullak-Ublick GA: The SLCO1A2 gene, encoding human organic anion-transporting polypeptide 1A2, is transactivated by the vitamin D receptor. Mol Pharmacol. 2012 Jul;82(1):37-46. doi: 10.1124/mol.112.077909. Epub 2012 Apr 3. [22474172 ]
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Has a D-25-hydroxylase activity on both forms of vitamin D, vitamin D(2) and D(3).
Gene Name:
CYP2R1
Uniprot ID:
Q6VVX0
Molecular Weight:
57358.82 Da
References
  1. Flanagan JN, Young MV, Persons KS, Wang L, Mathieu JS, Whitlatch LW, Holick MF, Chen TC: Vitamin D metabolism in human prostate cells: implications for prostate cancer chemoprevention by vitamin D. Anticancer Res. 2006 Jul-Aug;26(4A):2567-72. [16886665 ]
  2. Segura-Aguilar J: Peroxidase activity of liver microsomal vitamin D 25-hydroxylase and cytochrome P450 1A2 catalyzes 25-hydroxylation of vitamin D3 and oxidation of dopamine to aminochrome. Biochem Mol Med. 1996 Jun;58(1):122-9. [8809353 ]