Inecalcitol

Identification

Name
Inecalcitol
Accession Number
DB04796
Type
Small Molecule
Groups
Experimental, Investigational
Description
Not Available
Structure
Thumb
Synonyms
  • 19-nor-14-epi-23-yne-1,25 dihydroxyvitamin D3
  • 9,10-seco-14bh-19-norcholesta-5(z),7(e)-dien-1(r),3(r),25-triol-23-yne
External IDs
TX-522 / TX522
Categories
UNII
05FZV98342
CAS number
163217-09-2
Weight
Average: 400.603
Monoisotopic: 400.297745148
Chemical Formula
C26H40O3
InChI Key
HHGRMHMXKPQNGF-WNSNRMDMSA-N
InChI
InChI=1S/C26H40O3/c1-18(7-5-13-25(2,3)29)23-11-12-24-20(8-6-14-26(23,24)4)10-9-19-15-21(27)17-22(28)16-19/h9-10,18,21-24,27-29H,6-8,11-12,14-17H2,1-4H3/b20-10+/t18-,21-,22-,23-,24-,26-/m1/s1
IUPAC Name
(1R,3R)-5-{2-[(1R,3aR,4E,7aR)-1-[(2R)-6-hydroxy-6-methylhept-4-yn-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}cyclohexane-1,3-diol
SMILES

Pharmacology

Indication

Investigated for use/treatment in prostate cancer, psoriasis and hyperparathyroidism.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Inecalcitol is an analogue of calcitriol, the naturally active metabolite of vitamin D. Calcitriol and their analogues activate the vitamin D receptor (VDR). Vitamin D has a major role in regulating calcium absorption from the gut, storage in mineral form in the bones, and excretion by the kidney and effectively prevents rickets in infants. Vitamin D and calcitriol can cause hypercalcemia at high or frequently repeated doses; in turn, hypercalcemia can cause kidney toxicity by accumulation of calcium-containing micro-crystals and heart and muscle dysfunction by impairing contractions. [Hybrigenics Website] The mechanism of action is currently unknown, but it is proposed that inecalcitol exerts its superagonistic action through enhancing coactivator binding by the VDR.

TargetActionsOrganism
UVitamin D3 receptorNot AvailableHuman
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
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Wong MS, Delansorne R, Man RY, Vanhoutte PM: Vitamin D derivatives acutely reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H289-96. doi: 10.1152/ajpheart.00116.2008. Epub 2008 May 16. [PubMed:18487433]
  2. Eelen G, Verlinden L, Van Camp M, Claessens F, De Clercq P, Vandewalle M, Bouillon R, Verstuyf A: Altered Vitamin D receptor-coactivator interactions reflect superagonism of Vitamin D analogs. J Steroid Biochem Mol Biol. 2005 Oct;97(1-2):65-8. Epub 2005 Jul 20. [PubMed:16039117]
  3. Link [Link]
External Links
PubChem Compound
6915835
PubChem Substance
46504586
ChemSpider
5291648
ChEMBL
CHEMBL2105107
HET
TX5

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2RecruitingTreatmentAcute Myelogenous Leukaemia (AML)1
2RecruitingTreatmentCML, Chronic Phase1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00221 mg/mLALOGPS
logP4.97ALOGPS
logP4ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)14.67ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area60.69 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity121.57 m3·mol-1ChemAxon
Polarizability48.7 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9674
Blood Brain Barrier+0.8207
Caco-2 permeable+0.7691
P-glycoprotein substrateSubstrate0.7632
P-glycoprotein inhibitor INon-inhibitor0.6073
P-glycoprotein inhibitor IINon-inhibitor0.5706
Renal organic cation transporterNon-inhibitor0.8472
CYP450 2C9 substrateNon-substrate0.8131
CYP450 2D6 substrateNon-substrate0.9071
CYP450 3A4 substrateSubstrate0.7549
CYP450 1A2 substrateNon-inhibitor0.8627
CYP450 2C9 inhibitorNon-inhibitor0.809
CYP450 2D6 inhibitorNon-inhibitor0.9353
CYP450 2C19 inhibitorNon-inhibitor0.6117
CYP450 3A4 inhibitorNon-inhibitor0.6365
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5297
Ames testNon AMES toxic0.9107
CarcinogenicityNon-carcinogens0.8929
BiodegradationNot ready biodegradable1.0
Rat acute toxicity4.7066 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8707
hERG inhibition (predictor II)Non-inhibitor0.8772
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 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 / Ynones / Tertiary alcohols / Secondary alcohols / Cyclic alcohols and derivatives / Hydrocarbon derivatives
Substituents
Triterpenoid / Ynone / Tertiary alcohol / Cyclic alcohol / Secondary alcohol / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Alcohol / Aliphatic homopolycyclic compound
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
Vitamin D3 and derivatives (LMST03020649)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on September 11, 2007 11:49 / Updated on December 01, 2017 15:32