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Identification
NameDihydrotachysterol
Accession NumberDB01070  (APRD00143)
TypeSmall Molecule
GroupsApproved
Description

A vitamin D that can be regarded as a reduction product of vitamin D2. [PubChem]

Structure
Thumb
Synonyms
Anti-tetany substance 10
AT 10
Dihidrotaquisterol
Dihydrotachysterol
Dihydrotachysterolum
Vitamin D4
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hytakerolcapsule.125 mgoralSanofi Synthelabo Canada Inc1952-12-312003-07-30Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AtitenBayer
DihydralSolvay
DygratylDishman
TachystinChauvin
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIR5LM3H112R
CAS number67-96-9
WeightAverage: 398.6642
Monoisotopic: 398.354866094
Chemical FormulaC28H46O
InChI KeyInChIKey=ILYCWAKSDCYMBB-OPCMSESCSA-N
InChI
InChI=1S/C28H46O/c1-19(2)20(3)9-10-22(5)26-15-16-27-23(8-7-17-28(26,27)6)12-13-24-18-25(29)14-11-21(24)4/h9-10,12-13,19-22,25-27,29H,7-8,11,14-18H2,1-6H3/b10-9+,23-12+,24-13+/t20-,21-,22+,25-,26+,27-,28+/m0/s1
IUPAC Name
(1S,3E,4S)-3-{2-[(1R,3aS,4E,7aR)-1-[(2R,3E,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylcyclohexan-1-ol
SMILES
CC(C)[C@@H](C)\C=C\[C@@H](C)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1/C[C@@H](O)CC[C@@H]1C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as triterpenoids. These are terpene molecules containing 8 isoprene units.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassTriterpenoids
Direct ParentTriterpenoids
Alternative Parents
Substituents
  • Polycyclic triterpenoid
  • Triterpenoid
  • Steroid
  • Cyclohexanol
  • Cyclic alcohol
  • Secondary alcohol
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed for the prevention and treatment of rickets or osteomalacia, and to manage hypocalcemia associated with hypoparathyroidism or pseudohypoparathyroidism. Also used for the treatment of vitamin D dependent rickets, rickets or osteomalacia secondary to long-term high dose anticonvulsant therapy, early renal osteodystrophy, osteoporosis (in conjunction with calcium), and hypophosphatemia associated with Fanconi syndrome (with treatment of acidosis).
PharmacodynamicsDihydrotachysterol is hydroxylated in the liver to 25-hydroxydihydrotachysterol, which is the major circulating active form of the drug. It does not undergo further hydroxylation by the kidney and therefore is the analogue of 1, 25-dihydroxyvitamin D. Dihydrotachysterol is effective in the elevation of serum calcium by stimulating intestinal calcium absorption and mobilizing bone calcium in the absence of parathyroid hormone and of functioning renal tissue. Dihydrotachysterol also increases renal phosphate excretion.
Mechanism of actionOnce hydroxylated to 25-hydroxydihydrotachysterol, the modified drug binds to the vitamin D receptor. The bound form of the vitamin D receptor serves as a transcriptional regulator of bone matrix proteins, inducing the expression of osteocalcin and suppressing synthesis of type I collagen. Vitamin D (when bound to the vitamin D receptor)stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood. This stimulates intestinal calcium absorption and increases renal phosphate excretion. These are functions that are normally carried out by the parathyroid hormone.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding>99%
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityToxicity associated with dihydrotachysterol is similar to that seen with large doses of vitamin D.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9443
Caco-2 permeable+0.822
P-glycoprotein substrateSubstrate0.6576
P-glycoprotein inhibitor IInhibitor0.6558
P-glycoprotein inhibitor IINon-inhibitor0.8328
Renal organic cation transporterNon-inhibitor0.8051
CYP450 2C9 substrateNon-substrate0.817
CYP450 2D6 substrateNon-substrate0.8853
CYP450 3A4 substrateSubstrate0.7432
CYP450 1A2 substrateNon-inhibitor0.908
CYP450 2C9 inhibitorNon-inhibitor0.9053
CYP450 2D6 inhibitorNon-inhibitor0.9546
CYP450 2C19 inhibitorNon-inhibitor0.9027
CYP450 3A4 inhibitorNon-inhibitor0.8342
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7962
Ames testNon AMES toxic0.9236
CarcinogenicityNon-carcinogens0.9223
BiodegradationNot ready biodegradable0.9623
Rat acute toxicity3.1244 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8502
hERG inhibition (predictor II)Non-inhibitor0.708
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral.125 mg
Prices
Unit descriptionCostUnit
Dihydrotachysterol powder15.56USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP7.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000125 mg/mLALOGPS
logP7.86ALOGPS
logP7.4ChemAxon
logS-6.5ALOGPS
pKa (Strongest Acidic)18.3ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity129.11 m3·mol-1ChemAxon
Polarizability51.76 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
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
References
Synthesis Reference

von Werder, F.; U.S. Patent 2,228,491; January 14,1941; assigned to Winthrop Chemical
Company, Inc.

General References
  1. DeLuca HF: Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1689S-96S. [PubMed:15585789 ]
  2. Bosch R, Thijssen JH, Duursma SA: Action and metabolism of dihydrotachysterol2. J Steroid Biochem. 1987;27(4-6):829-36. [PubMed:3320562 ]
  3. Pierides AM: Pharmacology and therapeutic use of vitamin D and its analogues. Drugs. 1981 Apr;21(4):241-56. [PubMed:6262039 ]
External Links
ATC CodesA11CC02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolDihydrotachysterol may decrease the anticoagulant activities of Acenocoumarol.
AlfacalcidolThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Alfacalcidol.
Aluminum hydroxideThe serum concentration of Aluminum hydroxide can be increased when it is combined with Dihydrotachysterol.
AminophyllineThe serum concentration of Aminophylline can be increased when it is combined with Dihydrotachysterol.
BendroflumethiazideBendroflumethiazide may increase the hypercalcemic activities of Dihydrotachysterol.
BetamethasoneThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Betamethasone.
CalcipotriolThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Calcipotriol.
CalcitriolThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Calcitriol.
Calcium AcetateThe risk or severity of adverse effects can be increased when Calcium Acetate is combined with Dihydrotachysterol.
Calcium carbonateThe risk or severity of adverse effects can be increased when Calcium carbonate is combined with Dihydrotachysterol.
Calcium ChlorideThe risk or severity of adverse effects can be increased when Calcium Chloride is combined with Dihydrotachysterol.
Calcium citrateThe risk or severity of adverse effects can be increased when Calcium citrate is combined with Dihydrotachysterol.
Calcium gluconateThe risk or severity of adverse effects can be increased when Calcium gluconate is combined with Dihydrotachysterol.
ChlorothiazideChlorothiazide may increase the hypercalcemic activities of Dihydrotachysterol.
ChlorthalidoneChlorthalidone may increase the hypercalcemic activities of Dihydrotachysterol.
CholecalciferolThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Cholecalciferol.
CholestyramineThe serum concentration of Dihydrotachysterol can be decreased when it is combined with Cholestyramine.
ColesevelamThe serum concentration of Dihydrotachysterol can be decreased when it is combined with Colesevelam.
ColestipolThe serum concentration of Dihydrotachysterol can be decreased when it is combined with Colestipol.
DanazolDanazol may increase the hypercalcemic activities of Dihydrotachysterol.
DigoxinDihydrotachysterol may increase the arrhythmogenic activities of Digoxin.
DoxercalciferolThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Doxercalciferol.
ErgocalciferolThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Ergocalciferol.
HydrochlorothiazideHydrochlorothiazide may increase the hypercalcemic activities of Dihydrotachysterol.
IndapamideIndapamide may increase the hypercalcemic activities of Dihydrotachysterol.
MethyclothiazideMethyclothiazide may increase the hypercalcemic activities of Dihydrotachysterol.
MetolazoneMetolazone may increase the hypercalcemic activities of Dihydrotachysterol.
Mineral oilThe serum concentration of Dihydrotachysterol can be decreased when it is combined with Mineral oil.
NadololNadolol may increase the hypercalcemic activities of Dihydrotachysterol.
OrlistatThe serum concentration of Dihydrotachysterol can be decreased when it is combined with Orlistat.
ParicalcitolThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Paricalcitol.
SucralfateThe serum concentration of Sucralfate can be increased when it is combined with Dihydrotachysterol.
TheophyllineThe serum concentration of Theophylline can be increased when it is combined with Dihydrotachysterol.
WarfarinDihydrotachysterol may decrease the anticoagulant activities of Warfarin.
Food InteractionsNot Available

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
Molecular Weight:
48288.64 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Qaw F, Calverley MJ, Schroeder NJ, Trafford DJ, Makin HL, Jones G: In vivo metabolism of the vitamin D analog, dihydrotachysterol. Evidence for formation of 1 alpha,25- and 1 beta,25-dihydroxy-dihydrotachysterol metabolites and studies of their biological activity. J Biol Chem. 1993 Jan 5;268(1):282-92. [PubMed:8380156 ]
  4. Qaw FS, Makin HL, Jones G: Metabolism of 25-hydroxydihydrotachysterol3 in bone cells in vitro. Steroids. 1992 May;57(5):236-43. [PubMed:1336906 ]
  5. Gallagher JC, Sai AJ: Vitamin D insufficiency, deficiency, and bone health. J Clin Endocrinol Metab. 2010 Jun;95(6):2630-3. doi: 10.1210/jc.2010-0918. [PubMed:20525913 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23