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Identification
Name Alfacalcidol
Accession Number DB01436
Type small molecule
Groups approved, nutraceutical
Description

Alfacalcidol is an active metabolite of Vitamin D, which performs important functions in regulation of the calcium balance and the bone metabolism. Alfacalcidol is Vitamin D-hormone analog which is activated by the enzyme 25-hydroxylase in the liver for systemic and in osteoblasts for local D-hormone actions. It possesses a unique pattern of pleiotropic effects on, e.g. gut, bone, pararthyroids, muscle and brain. Alfacalcidol is superior to plain vitamin D (cholecalciferol) because the final kidney activation of the latter is regulated by a negative feedback mechanism. (PMID:17438884,17668216)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
1-hydroxycholecalciferol
1alpha-hydroxycholecalciferol
1alpha-hydroxyvitamin D3
Salts Not Available
Brand names
Name Company
Alsiodol
One Alpha
Brand mixtures Not Available
Categories
  • Bone Density Conservation Agents
CAS number 41294-56-8
Weight Average: 400.6371
Monoisotopic: 400.334130652
Chemical Formula C27H44O2
InChI Key InChIKey=OFHCOWSQAMBJIW-AVJTYSNKSA-N
InChI
InChI=1S/C27H44O2/c1-18(2)8-6-9-19(3)24-13-14-25-21(10-7-15-27(24,25)5)11-12-22-16-23(28)17-26(29)20(22)4/h11-12,18-19,23-26,28-29H,4,6-10,13-17H2,1-3,5H3/b21-11+,22-12-/t19-,23-,24-,25+,26+,27-/m1/s1
Plain Text
IUPAC Name
(1R,3S,5Z)-5-{2-[(1R,3aS,4E,7aR)-7a-methyl-1-[(2R)-6-methylheptan-2-yl]-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol
SMILES
CC(C)CCC[C@@H](C)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Isoprenes
  • Alcohols and Polyols
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Isoprenes
  • Alcohols and Polyols
Pharmacology
Indication Alfacalcidol is an active metabolite of Vitamin D, which performs important functions in regulation of the calcium balance and the bone metabolism.
Pharmacodynamics Alfacalcidol is Vitamin D-hormone analog which is activated by the enzyme 25-hydroxylase in the liver for systemic and in osteoblasts for local D-hormone actions.
Mechanism of action 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Hypercalcemia - 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.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Capsule Oral
Capsule Oral
Liquid Intravenous
Liquid Intravenous
Solution / drops Oral
Solution / drops Oral
Prices
Unit description Cost Unit
One-Alpha 2 mcg/ml 17.28 USD ml
One-Alpha 2 mcg/ml Drops 5.39 USD ml
One-Alpha 1 mcg Capsule 1.41 USD capsule
One-Alpha 0.25 mcg Capsule 0.47 USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 136 °C PhysProp
Predicted Properties
Property Value Source
water solubility 1.63e-03 g/l ALOGPS
logP 6.68 ALOGPS
logP 5.82 ChemAxon
logS -5.4 ALOGPS
pKa (strongest acidic) 14.39 ChemAxon
pKa (strongest basic) -2.8 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 40.46 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 124.7 ChemAxon
polarizability 50.55 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D01518 Link_out
PubChem Compound 5282181 Link_out
PubChem Substance 46505115 Link_out
ChemSpider 4445376 Link_out
PharmGKB PA164746469 Link_out
Drug Product Database 474517 Link_out
ATC Codes
  • A11CC03
AHFS Codes
  • 88:16.00
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Calcipotriol Vitamin D Analogs may enhance the adverse/toxic effect of other Vitamin D Analogs. Avoid combined use of multiple vitamin D analogs (at pharmacologic doses). Prescribing information for calcitriol, doxercalciferol, paricalcitol, and alfacalcidol each specifically cautions against such combined use.
Cholecalciferol Vitamin D analogs may enhance the adverse/toxic effect of other Vitamin D analogs. Avoid combined use of multiple vitamin D analogs (at pharmacologic doses). Prescribing information for calcitriol, doxercalciferol, paricalcitol, and alfacalcidol each specifically cautions against such combined use. Though not specified in the prescribing information for calcipotriene, cholecalciferol, and ergocalciferol, each contains warnings regarding the potential for vitamin D toxicity.
Colesevelam Bile acid sequestrants such as colesevelam may decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (e.g., cholestyramine). Monitor plasma calcium concentrations in patients receiving combined therapy with these agents. This is particularly important in patients receiving higher doses of a bile acid sequestant (i.e., 30 g/day or more of cholestyramine or equivalent) or in patients experiencing bile acid sequestrant-induced steatorrhea. Specific recommendations regarding the separation of administration of these agents are not defined; however, it would seem prudent to separate the administration of these agents by several hours to minimize the potential risk of interaction. Similar precautions do not apply to parenterally administered vitamin D analogs.
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
  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. Epub 2010 May 6. Pubmed

2. 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial

Pharmacological action: unknown

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

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

References:
  1. 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. Pubmed
Carriers

1. Vitamin D-binding protein

Actions: substrate

Multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid, and urine and on the surface of many cell types. In plasma, it carries the vitamin D sterols and prevents polymerization of actin by binding its monomers. DBP associates with membrane-bound immunoglobulin on the surface of B-lymphocytes and with IgG Fc receptor on the membranes of T-lymphocytes

UniProt ID: P02774 Link_out
Gene: GC Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
Comments
Drug created on July 26, 2007 06:34 / Updated on February 08, 2013 16:20