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Identification
NameCalcidiol
Accession NumberDB00146  (APRD00428, NUTR00006)
TypeSmall Molecule
GroupsApproved, 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
Synonyms
SynonymLanguageCode
(3beta,5Z,7e)-9,10-Secocholesta-5,7,10(19)-triene-3,25-diolNot AvailableNot Available
(3S,5Z,7e)-9,10-Secocholesta-5,7,10-triene-3,25-diolNot AvailableNot Available
(3β,5Z,7E)-9,10-secocholesta-5,7,10(19)-triene-3,25-diolNot AvailableNot Available
(5Z,7e)-(3S)-9,10-Secocholesta-5,7,10(19)-triene-3,25-diolNot AvailableNot Available
25-hydroxycholecalciferolNot AvailableNot Available
25-Hydroxyvitamin D3Not AvailableNot Available
25(OH)D3Not AvailableNot Available
3-{2-[1-(5-hydroxy-1,5-dimethyl-hexyl)-7a-methyl-octahydro-inden-4-ylidene]-ethylidene}-4-methylene-cyclohexanolNot AvailableNot Available
CalcidiolNot AvailableNot Available
CalcifediolNot AvailableINN
Calcifediol AnhydrousNot AvailableNot Available
CalcifediolumLatinINN
SaltsNot Available
Brand names
NameCompany
CalderolUpjohn
CaldiolMedica
De KaiChina Otsuka
DedrogylDesma
DédrogylDB
DidrogylBruno Farm.
HidroferolFaes
Brand mixturesNot Available
Categories
CAS number19356-17-3
WeightAverage: 400.6371
Monoisotopic: 400.334130652
Chemical FormulaC27H44O2
InChI KeyJWUBBDSIWDLEOM-DTOXIADCSA-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
IUPAC Name
(1S,3Z)-3-{2-[(1R,3aS,4E,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexan-1-ol
SMILES
C[C@H](CCCC(C)(C)O)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)CCC1=C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassVitamin D and Derivatives
Direct parentVitamin D and Derivatives
Alternative parentsSesterterpenes; Cyclohexanols; Tertiary Alcohols; Cyclic Alcohols and Derivatives; Polyamines
Substituentscyclohexanol; tertiary alcohol; cyclic alcohol; secondary alcohol; polyamine; alcohol
Classification descriptionThis compound belongs to the vitamin d and derivatives. These are compounds containing a secosteroid backbone, usually secoergostane or secocholestane.
Pharmacology
IndicationUsed 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.
PharmacodynamicsCalcidiol 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 actionCalcidiol 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.
AbsorptionReadily absorbed.
Volume of distributionNot Available
Protein bindingNot 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 eliminationNot Available
Half life288 hours
ClearanceNot Available
ToxicityBone 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9953
Blood Brain Barrier + 0.9164
Caco-2 permeable + 0.8891
P-glycoprotein substrate Substrate 0.7454
P-glycoprotein inhibitor I Inhibitor 0.5209
P-glycoprotein inhibitor II Inhibitor 0.6087
Renal organic cation transporter Non-inhibitor 0.7849
CYP450 2C9 substrate Non-substrate 0.8379
CYP450 2D6 substrate Non-substrate 0.9004
CYP450 3A4 substrate Substrate 0.7815
CYP450 1A2 substrate Non-inhibitor 0.8874
CYP450 2C9 substrate Non-inhibitor 0.9229
CYP450 2D6 substrate Non-inhibitor 0.9488
CYP450 2C19 substrate Non-inhibitor 0.7885
CYP450 3A4 substrate Non-inhibitor 0.7968
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.56
Ames test Non AMES toxic 0.8612
Carcinogenicity Non-carcinogens 0.917
Biodegradation Not ready biodegradable 0.991
Rat acute toxicity 4.1429 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8189
hERG inhibition (predictor II) Non-inhibitor 0.7589
Pharmacoeconomics
Manufacturers
  • Organon usa inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
TabletOral
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilityInsolubleNot Available
logP6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0022ALOGPS
logP6.71ALOGPS
logP5.65ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)18.38ChemAxon
pKa (Strongest Basic)-0.98ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity125.06 m3·mol-1ChemAxon
Polarizability50.32 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraGC-MS
References
Synthesis Reference

Dae-Jung Kang, Jong-Hyuk Im, Hyun-Jung Jung, Jae-Hoon Kang, “BUFFER COMPOSITION FOR CATALYZING THE PREPARATION OF CALCITRIOL OR CALCIFEDIOL AND METHOD FOR PREPARING CALCITRIOL OR CALCIFEDIOL USING SAME.” U.S. Patent US20120064584, issued March 15, 2012.

US20120064584
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC01561
ChEBI17933
ChEMBL
Therapeutic Targets DatabaseDAP000290
PharmGKBPA164745614
PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/vit_0265.shtml
WikipediaCalcidiol
ATC CodesA11CC06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Vitamin D3 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Vitamin D3 receptor P11473 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial O15528 Details

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. 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial Q07973 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 24, 2013 12:03