Identification

Name
Dihydrotachysterol
Accession Number
DB01070  (APRD00143)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • Anti-tetany substance 10
  • Dihidrotaquisterol
  • Dihydrotachysterolum
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
HytakerolCapsule.125 mgOralSanofi Synthelabo1952-12-312003-07-30Canada
International/Other Brands
AT 10 / Atiten (Bayer) / Dihydral (Solvay) / Dygratyl (Dishman) / Tachystin (Chauvin)
Categories
UNII
R5LM3H112R
CAS number
67-96-9
Weight
Average: 398.6642
Monoisotopic: 398.354866094
Chemical Formula
C28H46O
InChI Key
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

Pharmacology

Indication

Used 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).

Structured Indications
Not Available
Pharmacodynamics

Dihydrotachysterol 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 action

Once 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.

TargetActionsOrganism
AVitamin D3 receptor
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

>99%

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Toxicity associated with dihydrotachysterol is similar to that seen with large doses of vitamin D.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinDihydrotachysterol may increase the arrhythmogenic activities of Acetyldigitoxin.Approved
AcetyldigoxinDihydrotachysterol may increase the arrhythmogenic activities of Acetyldigoxin.Experimental
Aluminum hydroxideThe serum concentration of Aluminum hydroxide can be increased when it is combined with Dihydrotachysterol.Approved
BendroflumethiazideBendroflumethiazide may increase the hypercalcemic activities of Dihydrotachysterol.Approved
CalcidiolThe risk or severity of adverse effects can be increased when Calcidiol is combined with Dihydrotachysterol.Approved, Nutraceutical
CalcipotriolThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Calcipotriol.Approved
Calcium AcetateThe risk or severity of adverse effects can be increased when Calcium Acetate is combined with Dihydrotachysterol.Approved
Calcium CarbonateThe risk or severity of adverse effects can be increased when Calcium Carbonate is combined with Dihydrotachysterol.Approved
Calcium ChlorideThe risk or severity of adverse effects can be increased when Calcium Chloride is combined with Dihydrotachysterol.Approved
Calcium CitrateThe risk or severity of adverse effects can be increased when Calcium Citrate is combined with Dihydrotachysterol.Approved
Calcium glubionateThe risk or severity of adverse effects can be increased when Calcium glubionate is combined with Dihydrotachysterol.Approved
Calcium GluceptateThe risk or severity of adverse effects can be increased when Calcium Gluceptate is combined with Dihydrotachysterol.Approved
Calcium gluconateThe risk or severity of adverse effects can be increased when Calcium gluconate is combined with Dihydrotachysterol.Approved, Vet Approved
Calcium lactateThe risk or severity of adverse effects can be increased when Calcium lactate is combined with Dihydrotachysterol.Approved, Experimental, Investigational, Vet Approved
Calcium lactate gluconateThe risk or severity of adverse effects can be increased when Calcium lactate gluconate is combined with Dihydrotachysterol.Experimental
Calcium laevulateThe risk or severity of adverse effects can be increased when Calcium laevulate is combined with Dihydrotachysterol.Experimental
Calcium pangamateThe risk or severity of adverse effects can be increased when Calcium pangamate is combined with Dihydrotachysterol.Experimental
Calcium PhosphateThe risk or severity of adverse effects can be increased when Calcium Phosphate is combined with Dihydrotachysterol.Approved
CaseinThe risk or severity of adverse effects can be increased when Casein is combined with Dihydrotachysterol.Approved
ChlorothiazideChlorothiazide may increase the hypercalcemic activities of Dihydrotachysterol.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypercalcemic activities of Dihydrotachysterol.Approved
CholestyramineThe serum concentration of Dihydrotachysterol can be decreased when it is combined with Cholestyramine.Approved
ColesevelamThe serum concentration of Dihydrotachysterol can be decreased when it is combined with Colesevelam.Approved
ColestipolThe serum concentration of Dihydrotachysterol can be decreased when it is combined with Colestipol.Approved
CyclopenthiazideCyclopenthiazide may increase the hypercalcemic activities of Dihydrotachysterol.Experimental
CymarinDihydrotachysterol may increase the arrhythmogenic activities of Cymarin.Experimental
DanazolDanazol may increase the hypercalcemic activities of Dihydrotachysterol.Approved
DeslanosideDihydrotachysterol may increase the arrhythmogenic activities of Deslanoside.Approved
DigitoxinDihydrotachysterol may increase the arrhythmogenic activities of Digitoxin.Approved, Investigational
DigoxinDihydrotachysterol may increase the arrhythmogenic activities of Digoxin.Approved
Digoxin Immune Fab (Ovine)Dihydrotachysterol may increase the arrhythmogenic activities of Digoxin Immune Fab (Ovine).Approved
DoxercalciferolThe risk or severity of adverse effects can be increased when Doxercalciferol is combined with Dihydrotachysterol.Approved
ErgocalciferolThe risk or severity of adverse effects can be increased when Ergocalciferol is combined with Dihydrotachysterol.Approved, Nutraceutical
GitoformateDihydrotachysterol may increase the arrhythmogenic activities of Gitoformate.Experimental
HydrochlorothiazideHydrochlorothiazide may increase the hypercalcemic activities of Dihydrotachysterol.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypercalcemic activities of Dihydrotachysterol.Approved, Investigational
IndapamideIndapamide may increase the hypercalcemic activities of Dihydrotachysterol.Approved
Lanatoside CDihydrotachysterol may increase the arrhythmogenic activities of Lanatoside C.Experimental
MethyclothiazideMethyclothiazide may increase the hypercalcemic activities of Dihydrotachysterol.Approved
MetildigoxinDihydrotachysterol may increase the arrhythmogenic activities of Metildigoxin.Experimental
MetolazoneMetolazone may increase the hypercalcemic activities of Dihydrotachysterol.Approved
Mineral oilThe serum concentration of Dihydrotachysterol can be decreased when it is combined with Mineral oil.Approved, Vet Approved
OleandrinDihydrotachysterol may increase the arrhythmogenic activities of Oleandrin.Experimental, Investigational
OrlistatThe serum concentration of Dihydrotachysterol can be decreased when it is combined with Orlistat.Approved, Investigational
OuabainDihydrotachysterol may increase the arrhythmogenic activities of Ouabain.Approved
ParicalcitolThe risk or severity of adverse effects can be increased when Paricalcitol is combined with Dihydrotachysterol.Approved, Investigational
PeruvosideDihydrotachysterol may increase the arrhythmogenic activities of Peruvoside.Experimental
PolythiazidePolythiazide may increase the hypercalcemic activities of Dihydrotachysterol.Approved
ProscillaridinDihydrotachysterol may increase the arrhythmogenic activities of Proscillaridin.Experimental
QuinethazoneQuinethazone may increase the hypercalcemic activities of Dihydrotachysterol.Approved
SucralfateThe serum concentration of Sucralfate can be increased when it is combined with Dihydrotachysterol.Approved
TrichlormethiazideTrichlormethiazide may increase the hypercalcemic activities of Dihydrotachysterol.Approved, Vet Approved
Food Interactions
Not 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]
  4. Gagnon R, Ogden GW, Just G, Kaye M: Comparison of dihydrotachysterol and 5,6-trans vitamin D3 on intestinal calcium absorption in patients with chronic renal failure. Can J Physiol Pharmacol. 1974 Apr;52(2):272-4. [PubMed:4365509]
External Links
Human Metabolome Database
HMDB15203
KEGG Drug
D00299
KEGG Compound
C06957
PubChem Compound
5311071
PubChem Substance
46507699
ChemSpider
4470607
ChEBI
4591
ChEMBL
CHEMBL2356023
Therapeutic Targets Database
DAP000365
PharmGKB
PA164744345
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dihydrotachysterol
ATC Codes
A11CC02 — Dihydrotachysterol

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not 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.
Patents
Not Available

Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Vitamin D and derivatives
Direct Parent
Vitamin D and derivatives
Alternative Parents
Triterpenoids / Secondary alcohols / Cyclic alcohols and derivatives / Hydrocarbon derivatives
Substituents
Triterpenoid / Cyclic alcohol / Secondary alcohol / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Alcohol / Aliphatic homopolycyclic compound
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
hydroxy seco-steroid, seco-ergostane, vitamin D (CHEBI:4591) / Vitamin D2 and derivatives (LMST03010056)

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...
Gene Name
VDR
Uniprot ID
P11473
Uniprot Name
Vitamin D3 receptor
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]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:46