Identification
NameAlfacalcidol
Accession NumberDB01436
TypeSmall Molecule
GroupsApproved, 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
Synonyms
(5Z,7e)-9,10-Seco-5,7,10(19)-cholestatrien-1alpha,3beta-diol
1-hydroxycholecalciferol
1alpha-Hydroxy-vitamin D3
1alpha-hydroxycholecalciferol
1alpha-hydroxyvitamin D3
9,10-Secocholesta-5,7,10(19)-triene-1alpha,3beta-diol
Alfacalcidolum
Alsiodol
External IDs Not Available
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
One Alpha Caps 0.25mcgCapsule0.25 mcgOralLeo Pharma1980-12-31Not applicableCanada
One Alpha Caps 1mcgCapsule1 mcgOralLeo Pharma1980-12-31Not applicableCanada
One-alphaSolution / drops2 mcgOralLeo Pharma2000-12-04Not applicableCanada
One-alphaLiquid2 mcgIntravenousLeo Pharma2001-02-20Not applicableCanada
One-alphaCapsule0.5 mcgOralLeo PharmaNot applicableNot applicableCanada
One-alpha Sol 0.2mcg/mlLiquid.2 mcgOralLeo Pharma1989-12-312000-12-04Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AlsiodolNot Available
One AlphaNot Available
Brand mixturesNot Available
Categories
UNIIURQ2517572
CAS number41294-56-8
WeightAverage: 400.6371
Monoisotopic: 400.334130652
Chemical FormulaC27H44O2
InChI KeyOFHCOWSQAMBJIW-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
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[[email protected]](O)C1=C
Pharmacology
Indication

Alfacalcidol is an active metabolite of Vitamin D, which performs important functions in regulation of the calcium balance and the bone metabolism.

Structured Indications
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Vitamin D3 receptorProteinyes
agonist
HumanP11473 details
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrialProteinunknownNot AvailableHumanO15528 details
Retinoic acid receptor RXR-alphaProteinunknownNot AvailableHumanP19793 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot 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
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAlfacalcidol may increase the arrhythmogenic activities of Acetyldigitoxin.Approved
Aluminum hydroxideThe serum concentration of Aluminum hydroxide can be increased when it is combined with Alfacalcidol.Approved
BendroflumethiazideBendroflumethiazide may increase the hypercalcemic activities of Alfacalcidol.Approved
CalcidiolThe risk or severity of adverse effects can be increased when Calcidiol is combined with Alfacalcidol.Approved, Nutraceutical
CalcipotriolThe risk or severity of adverse effects can be increased when Alfacalcidol is combined with Calcipotriol.Approved
CalcitriolThe risk or severity of adverse effects can be increased when Calcitriol is combined with Alfacalcidol.Approved, Nutraceutical
CalciumThe risk or severity of adverse effects can be increased when Calcium is combined with Alfacalcidol.Nutraceutical
Calcium AcetateThe risk or severity of adverse effects can be increased when Calcium Acetate is combined with Alfacalcidol.Approved
Calcium CarbonateThe risk or severity of adverse effects can be increased when Calcium carbonate is combined with Alfacalcidol.Approved
Calcium ChlorideThe risk or severity of adverse effects can be increased when Calcium Chloride is combined with Alfacalcidol.Approved
Calcium CitrateThe risk or severity of adverse effects can be increased when Calcium citrate is combined with Alfacalcidol.Approved
Calcium glubionateThe risk or severity of adverse effects can be increased when Calcium glubionate is combined with Alfacalcidol.Approved
Calcium GluceptateThe risk or severity of adverse effects can be increased when Calcium Gluceptate is combined with Alfacalcidol.Approved
Calcium gluconateThe risk or severity of adverse effects can be increased when Calcium gluconate is combined with Alfacalcidol.Approved, Vet Approved
ChlorothiazideChlorothiazide may increase the hypercalcemic activities of Alfacalcidol.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypercalcemic activities of Alfacalcidol.Approved
CholecalciferolThe risk or severity of adverse effects can be increased when Cholecalciferol is combined with Alfacalcidol.Approved, Nutraceutical
CholestyramineThe serum concentration of Alfacalcidol can be decreased when it is combined with Cholestyramine.Approved
ColesevelamThe serum concentration of Alfacalcidol can be decreased when it is combined with Colesevelam.Approved
ColestipolThe serum concentration of Alfacalcidol can be decreased when it is combined with Colestipol.Approved
DanazolDanazol may increase the hypercalcemic activities of Alfacalcidol.Approved
DeslanosideAlfacalcidol may increase the arrhythmogenic activities of Deslanoside.Approved
DigitoxinAlfacalcidol may increase the arrhythmogenic activities of Digitoxin.Approved
DigoxinAlfacalcidol may increase the arrhythmogenic activities of Digoxin.Approved
DihydrotachysterolThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Alfacalcidol.Approved
DoxercalciferolThe risk or severity of adverse effects can be increased when Alfacalcidol is combined with Doxercalciferol.Approved
ErgocalciferolThe risk or severity of adverse effects can be increased when Ergocalciferol is combined with Alfacalcidol.Approved, Nutraceutical
HydrochlorothiazideHydrochlorothiazide may increase the hypercalcemic activities of Alfacalcidol.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypercalcemic activities of Alfacalcidol.Approved
IndapamideIndapamide may increase the hypercalcemic activities of Alfacalcidol.Approved
Magnesium HydroxideThe serum concentration of Magnesium hydroxide can be increased when it is combined with Alfacalcidol.Approved
Magnesium oxideThe serum concentration of Magnesium oxide can be increased when it is combined with Alfacalcidol.Approved
Magnesium salicylateThe serum concentration of Magnesium salicylate can be increased when it is combined with Alfacalcidol.Approved
Magnesium SulfateThe serum concentration of Magnesium Sulfate can be increased when it is combined with Alfacalcidol.Approved, Vet Approved
MethyclothiazideMethyclothiazide may increase the hypercalcemic activities of Alfacalcidol.Approved
MetolazoneMetolazone may increase the hypercalcemic activities of Alfacalcidol.Approved
OleandrinAlfacalcidol may increase the arrhythmogenic activities of Anvirzel.Experimental
OrlistatThe serum concentration of Alfacalcidol can be decreased when it is combined with Orlistat.Approved, Investigational
OuabainAlfacalcidol may increase the arrhythmogenic activities of Ouabain.Approved
ParicalcitolThe risk or severity of adverse effects can be increased when Alfacalcidol is combined with Paricalcitol.Approved, Investigational
PolythiazidePolythiazide may increase the hypercalcemic activities of Alfacalcidol.Approved
QuinethazoneQuinethazone may increase the hypercalcemic activities of Alfacalcidol.Approved
SucralfateThe serum concentration of Sucralfate can be increased when it is combined with Alfacalcidol.Approved
TrichlormethiazideTrichlormethiazide may increase the hypercalcemic activities of Alfacalcidol.Approved, Vet Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesA11CC03 — AlfacalcidolM05BB06 — Alendronic acid and alfacalcidol, sequential
AHFS Codes
  • 88:16.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentGraves Diseases1
2RecruitingTreatmentAutosomal Dominant Hypocalcemia / Autosomal Dominant Hypocalcemia or OR Primary Hypoparathyroidism Related to Other Cause But Complicated by Hypercalciuria Under Treatment1
2Unknown StatusTreatmentCalcifications, Vascular1
3CompletedTreatmentMuscle Weakness1
3CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
3CompletedTreatmentBone destruction1
4CompletedTreatmentEnd Stage Renal Disease (ESRD) / Hyperparathyroidism, Secondary1
4CompletedTreatmentFalls / Osteopenia / Postmenopausal Osteoporosis (PMO)1
4CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
4Not Yet RecruitingTreatmentGlomerulonephritis minimal lesion1
4RecruitingTreatmentType 2 Diabetic Nephropathy1
4Unknown StatusTreatmentBone destruction1
4WithdrawnPreventionAgeing / Chronic Renal Insufficiency / Falls, Accidental1
Not AvailableCompletedTreatmentAlfacalcidol, Secondary Hyperparathyroidism, Hemodialysis1
Not AvailableCompletedTreatmentHyperparathyroidism, Secondary1
Not AvailableRecruitingTreatmentBone destruction1
Not AvailableTerminatedTreatmentChronic Kidney Disease (CKD) / Deficiency, Vitamin D / Hyperparathyroidism, Secondary1
Not AvailableUnknown StatusTreatmentArthroplasty, Replacement, Hip / Bone Density1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
CapsuleOral0.25 mcg
CapsuleOral1 mcg
CapsuleOral0.5 mcg
LiquidIntravenous2 mcg
Solution / dropsOral2 mcg
LiquidOral.2 mcg
Prices
Unit descriptionCostUnit
One-Alpha 2 mcg/ml17.28USD ml
One-Alpha 2 mcg/ml Drops5.39USD ml
One-Alpha 1 mcg Capsule1.41USD capsule
One-Alpha 0.25 mcg Capsule0.47USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)136 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.00163 mg/mLALOGPS
logP6.68ALOGPS
logP5.82ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)14.39ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity124.7 m3·mol-1ChemAxon
Polarizability50.55 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9865
Blood Brain Barrier+0.9142
Caco-2 permeable+0.7866
P-glycoprotein substrateSubstrate0.7469
P-glycoprotein inhibitor INon-inhibitor0.5785
P-glycoprotein inhibitor IIInhibitor0.5574
Renal organic cation transporterNon-inhibitor0.7945
CYP450 2C9 substrateNon-substrate0.8188
CYP450 2D6 substrateNon-substrate0.8945
CYP450 3A4 substrateSubstrate0.7656
CYP450 1A2 substrateNon-inhibitor0.8249
CYP450 2C9 inhibitorNon-inhibitor0.8802
CYP450 2D6 inhibitorNon-inhibitor0.9434
CYP450 2C19 inhibitorNon-inhibitor0.7466
CYP450 3A4 inhibitorNon-inhibitor0.8596
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5436
Ames testNon AMES toxic0.9077
CarcinogenicityNon-carcinogens0.9003
BiodegradationNot ready biodegradable0.9944
Rat acute toxicity4.6023 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7959
hERG inhibition (predictor II)Non-inhibitor0.8176
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as vitamin d and derivatives. These 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 ParentsTriterpenoids / Secondary alcohols / Cyclic alcohols and derivatives / Hydrocarbon derivatives
SubstituentsTriterpenoid / Cyclic alcohol / Secondary alcohol / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Alcohol / Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptorsdiol, seco-cholestane, D3 vitamins, hydroxycalciol (CHEBI:31186 ) / Vitamin D3 and derivatives (LMST03020231 )

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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
Uniprot Name:
Vitamin D3 receptor
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. [PubMed:15503649 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed: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. [PubMed:20435140 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Iron ion binding
Specific Function:
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.
Gene Name:
CYP27B1
Uniprot ID:
O15528
Uniprot Name:
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
Molecular Weight:
56503.475 Da
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:15369780 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXR...
Gene Name:
RXRA
Uniprot ID:
P19793
Uniprot Name:
Retinoic acid receptor RXR-alpha
Molecular Weight:
50810.835 Da
References
  1. Zhang J, Chalmers MJ, Stayrook KR, Burris LL, Garcia-Ordonez RD, Pascal BD, Burris TP, Dodge JA, Griffin PR: Hydrogen/deuterium exchange reveals distinct agonist/partial agonist receptor dynamics within vitamin D receptor/retinoid X receptor heterodimer. Structure. 2010 Oct 13;18(10):1332-41. doi: 10.1016/j.str.2010.07.007. [PubMed:20947021 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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
Uniprot Name:
Vitamin D-binding protein
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:8759764 ]
Drug created on July 26, 2007 06:34 / Updated on August 02, 2017 16:33