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Identification
Name Calcidiol
Accession Number DB00146 (APRD00428, NUTR00006)
Type small molecule
Groups approved, nutraceutical
Description

The major circulating metabolite of vitamin D3 (cholecalciferol). It is produced in the liver and is the best indicator of the body’s vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Calcifediol
  • Calcifediol Anhydrous
  • Calcifediolum [INN-Latin]
  • Calcifidiol
Brand names
  • Calderol
  • Delakmin
Brand name mixtures Not Available
Categories
  • Antihypocalcemic Agents
  • Antihypoparathyroid Agents
  • Vitamins (Vitamin D)
  • Bone Density Conservation Agents
  • Vitamins
CAS number 19356-17-3
Weight Average: 400.6371
Monoisotopic: 400.334130652
Chemical Formula C27H44O2
InChI Key InChIKey=JWUBBDSIWDLEOM-BNQRRPJDSA-N
InChI
InChI=1S/C27H44O2/c1-19-10-13-23(28)18-22(19)12-11-21-9-7-17-27(5)24(14-15-25(21)27)20(2)8-6-16-26(3,4)29/h11-12,20,23-25,28-29H,1,6-10,13-18H2,2-5H3/b21-11+,22-12-/t20-,23-,24-,25?,27-/m1/s1
Plain Text
IUPAC Name
(1R,3Z)-3-{2-[(1R,4E,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexan-1-ol
SMILES
[H][C@@]1(CCC2[C@]1(C)CCC\C2=C/C=C1/C[C@H](O)CCC1=C)[C@H](C)CCCC(C)(C)O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Alcohols and Polyols
  • Isoprenes
Pharmacology
Indication Used to treat 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.
Pharmacodynamics Calcidiol is the precursor of vitamin D3. Vitamin D3 is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of vitamin A. The classical manifestations of vitamin D deficiency is rickets, which is seen in children and results in bony deformaties including bowed long bones. Deficiency in adults leads to the disease osteomalacia. Both rickets and osteomalacia reflect impaired mineralization of newly synthesized bone matrix, and usually result from a combination of inadequate exposure to sunlight and decreased dietary intake of vitamin D. Common causes of vitamin D deficiency include genetic defects in the vitamin D receptor, severe liver or kidney disease, and insufficient exposure to sunlight. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma.
Mechanism of action Calcidiol is transformed in the kidney by 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to calcitriol, 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.
Absorption Readily absorbed.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Calcidiol undergoes hydroxylation in the mitochondria of kidney tissue, and this reaction is activated by the renal 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to produce calcitriol (1,25- dihydroxycholecalciferol), the active form of vitamin D3.
Route of elimination Not Available
Half life 288 hours
Clearance Not Available
Toxicity Bone pain, constipation (especially in children or adolescents), diarrhea, drowsiness, dryness of mouth; headache (continuing), increased thirst, increase in frequency of urination, especially at night, or in amount of urine, irregular heartbeat, itching skin, loss of appetite, metallic taste, muscle pain, nausea or vomiting (especially in children or adolescents), unusual tiredness or weakness.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Organon usa inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Tablet Oral
Prices Not Available
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility Insoluble PhysProp
logP 6 PhysProp
Predicted Properties
Property Value Source
water solubility 2.20e-03 g/l ALOGPS
logP 6.71 ALOGPS
logP 5.65 ChemAxon Molconvert
logS -5.26 ALOGPS
pKa 18.53 ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 40.46 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 125.06 ChemAxon Molconvert
polarizability 50.15 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C01561 Link_out
PubChem Compound 6433735 Link_out
PubChem Substance 46505690 Link_out
ChemSpider 4938806 Link_out
ChEBI 17933 Link_out
ChEMBL 17933 Link_out
Therapeutic Targets Database DAP000290 Link_out
PharmGKB PA452501 Link_out
Drug Product Database 0 Link_out
PDRhealth http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/vit_0265.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Calcidiol Link_out
ATC Codes
  • A11CC06
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Vitamin D3 receptor

Pharmacological action: yes
Actions: agonist

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

References:
  1. Reinhart GA: Vitamin D analogs: novel therapeutic agents for cardiovascular disease? Curr Opin Investig Drugs. 2004 Sep;5(9):947-51. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial

Actions: substrate

Catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D) to 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D) plays an important role in normal bone growth, calcium metabolism, and tissue differentiation

UniProt ID: O15528 Link_out
Gene: CYP27B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Schuster I: Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta. 2010 Jul 7. Pubmed
  2. Bernad M, Jaramillo G, Aguado P, del Campo T, Coya J, Martin Mola E, Gijon Banos J, Saldana Barrera H, Martinez ME: [Polymorphism of the gene of vitamin D receptor and bone mineral density in postmenopausal women] Med Clin (Barc). 1999 May 15;112(17):651-5. Pubmed
  3. Diesel B, Radermacher J, Bureik M, Bernhardt R, Seifert M, Reichrath J, Fischer U, Meese E: Vitamin D(3) metabolism in human glioblastoma multiforme: functionality of CYP27B1 splice variants, metabolism of calcidiol, and effect of calcitriol. Clin Cancer Res. 2005 Aug 1;11(15):5370-80. Pubmed
  4. Eto TA, Nakamura Y, Taniguchi T, Miyamoto K, Nagatomo J, Maeda Y, Higashi S, Okuda K, Setoguchi T: Assay of 25-hydroxyvitamin D3 1 alpha-hydroxylase in rat kidney mitochondria. Anal Biochem. 1998 Apr 10;258(1):53-8. Pubmed
  5. Hart GR, Furniss JL, Laurie D, Durham SK: Measurement of vitamin D status: background, clinical use, and methodologies. Clin Lab. 2006;52(7-8):335-43. Pubmed
  6. Vigo Gago E, Cadarso-Suarez C, Perez-Fernandez R, Romero Burgos R, Devesa Mugica J, Segura Iglesias C: Association between vitamin D receptor FokI. Polymorphism and serum parathyroid hormone level in patients with chronic renal failure. J Endocrinol Invest. 2005 Feb;28(2):117-21. Pubmed

2. Cytochrome P450 24A1, mitochondrial

Actions: substrate

Has a role in maintaining calcium homeostasis. Catalyzes the NADPH-dependent 24-hydroxylation of 25-hydroxyvitamin D(3) in the presence of adrenodoxin and NADPH-adrenodoxin reductase

UniProt ID: Q07973 Link_out
Gene: CYP24A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:36

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.