Dihydrotachysterol

Identification

Summary

Dihydrotachysterol is a synthetic analog of vitamin D that does not require renal activation like vitamin D2 or Vitamin D3.

Generic Name
Dihydrotachysterol
DrugBank Accession Number
DB01070
Background

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

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 398.6642
Monoisotopic: 398.354866094
Chemical Formula
C28H46O
Synonyms
  • Anti-tetany substance 10
  • Dihidrotaquisterol
  • Dihydrotachysterol
  • Dihydrotachysterolum

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).

Pharmacology
Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
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
Humans
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

Adverse Effects
Adverseeffects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

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

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcetyldigitoxinThe risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Dihydrotachysterol is combined with Acetyldigitoxin.
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.
Beclomethasone dipropionateThe therapeutic efficacy of Dihydrotachysterol can be decreased when used in combination with Beclomethasone dipropionate.
BendroflumethiazideThe risk or severity of hypercalcemia can be increased when Bendroflumethiazide is combined with Dihydrotachysterol.
BenzthiazideThe risk or severity of hypercalcemia can be increased when Benzthiazide is combined with Dihydrotachysterol.
BetamethasoneThe therapeutic efficacy of Dihydrotachysterol can be decreased when used in combination with Betamethasone.
Betamethasone phosphateThe therapeutic efficacy of Dihydrotachysterol can be decreased when used in combination with Betamethasone phosphate.
BudesonideThe therapeutic efficacy of Dihydrotachysterol can be decreased when used in combination with Budesonide.
CalcifediolThe risk or severity of adverse effects can be increased when Calcifediol is combined with Dihydrotachysterol.
Interactions
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
No interactions found.

Products

Products2
Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
AT 10 / Atiten (Bayer) / Dihydral (Solvay) / Dygratyl (Dishman) / Tachystin (Chauvin)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
HytakerolCapsule.125 mgOralSanofi Synthelabo1952-12-312003-07-30Canada flag

Categories

ATC Codes
A11CC02 — Dihydrotachysterol
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Alcohol / Aliphatic homopolycyclic compound / Cyclic alcohol / Hydrocarbon derivative / Organic oxygen compound / Organooxygen compound / Secondary alcohol / Triterpenoid
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
hydroxy seco-steroid, seco-ergostane, vitamin D (CHEBI:4591) / Vitamin D2 and derivatives (LMST03010056)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
R5LM3H112R
CAS number
67-96-9
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
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

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. [Article]
  2. Bosch R, Thijssen JH, Duursma SA: Action and metabolism of dihydrotachysterol2. J Steroid Biochem. 1987;27(4-6):829-36. [Article]
  3. Pierides AM: Pharmacology and therapeutic use of vitamin D and its analogues. Drugs. 1981 Apr;21(4):241-56. [Article]
  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. [Article]
  5. Codifa: Atiten (dihydrotachisterol) oral drops [Link]
Human Metabolome Database
HMDB0015203
KEGG Drug
D00299
KEGG Compound
C06957
PubChem Compound
5311071
PubChem Substance
46507699
ChemSpider
4470607
RxNav
3429
ChEBI
4591
ChEMBL
CHEMBL2356023
ZINC
ZINC000004212953
Therapeutic Targets Database
DAP000365
PharmGKB
PA164744345
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dihydrotachysterol

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAdvanced Malignant Glioma1
2CompletedTreatmentAdvanced Renal Cell Carcinoma (aRCC)1
2WithdrawnTreatmentParkinson's Disease (PD)1
1CompletedNot AvailableHealthy Subjects (HS)2
1CompletedBasic SciencePoliomyelitis / Tropical Enteropathy1
Not AvailableCompletedPreventionFollicular Tonsillitis (Chronic)1
Not AvailableCompletedTreatmentThrombotic events1
Not AvailableRecruitingTreatmentEctasia / Keratoconus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Murfreesboro Pharmaceutical Nursing Supply
  • Professional Co.
  • Sanofi-Aventis Inc.
Dosage Forms
FormRouteStrength
CapsuleOral0.5 mg
SolutionOral1 mg/mL
Solution / dropsOral1 MG/ML
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

Targets

Drugtargets2
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  4. Qaw FS, Makin HL, Jones G: Metabolism of 25-hydroxydihydrotachysterol3 in bone cells in vitro. Steroids. 1992 May;57(5):236-43. [Article]
  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. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created on June 13, 2005 13:24 / Updated on June 12, 2021 10:52