Identification

Name
Calcitriol
Accession Number
DB00136  (NUTR00003, APRD00246, DB05314)
Type
Small Molecule
Groups
Approved, Nutraceutical
Description

Calcitriol or 1,25-dihydroxycholecalciferol (abbreviated 1,25-(OH)2-D3) is the active form of vitamin D found in the body (vitamin D3). Calcitriol is marketed under various trade names including Rocaltrol (Roche), Calcijex (Abbott) and Decostriol (Mibe, Jesalis). It is produced in the kidneys via 25-hydroxyvitamin D-1 α-hydroxylase by conversion from 25-hydroxycholecalciferol (calcidiol). This is stimulated by a decrease in serum calcium, phosphate (PO43−) and parathyroid hormone (PTH) levels. It regulates calcium levels by increasing the absorption of calcium and phosphate from the gastrointestinal tract, increasing calcium and phosphate reabsorption in the kidneys and inhibiting the release of PTH. Calcitriol is also commonly used as a medication in the treatment of hypocalcemia and osteoporosis.

Structure
Thumb
Synonyms
  • (1S,3R,5Z,7E)-9,10-secocholesta-5,7,10-triene-1,3,25-triol
  • (1α,3β,5Z,7E)-9,10-secocholesta-5,7,10(19)-triene-1,3,25-triol
  • (5Z,7E)-(1S,3R)-9,10-secocholesta-5,7,10(19)-triene-1,3,25-triol
  • 1-alpha-25-Dihydroxyvitamin D3
  • 1,25-DHCC
  • 1,25-dihydroxycholecalciferol
  • 1α,25-dihydroxycholecalciferol
  • 1α,25-dihydroxyvitamin D3
  • 1α,25(OH)2D3
  • Calcitriol
  • Calcitriolum
External IDs
DN-101 / RO 21-5535 / RO-21-5535 / RO-215535
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CalcijexSolution2 mcgIntravenousAbbvie1990-12-312017-01-13Canada
CalcijexInjection, solution1 ug/1mLIntravenousAbbvie2010-06-012012-08-01Us
CalcijexSolution1 mcgIntravenousAbbvie1990-12-312017-01-13Canada
CalcitriolSolution1 ug/1mLIntravenousNEPHRX, LLC2009-01-27Not applicableUs
CalcitriolInjection, solution2 ug/1mLIntravenousAMERICAN REGENT, INC.2007-01-012007-01-01Us
CalcitriolOintment3 ug/1gTopicalPerrigo New York Inc.2012-03-08Not applicableUs
Calcitriol InjectionSolution1 mcgIntravenousFresenius Kabi2003-07-07Not applicableCanada
Calcitriol Injection USPSolution1 mcgIntravenousSterimax Inc2015-03-27Not applicableCanada
Calcitriol Injection USPSolution2 mcgIntravenousSterimax Inc2015-04-16Not applicableCanada
Calcitriol-odanCapsule0.25 mcgOralOdan Laboratories Ltd2014-10-10Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CalcitriolCapsule, liquid filled0.25 ug/1OralKaiser Foundations Hospitals2018-07-26Not applicableUs
CalcitriolInjection, solution1 mg/1mLIntravenousPhysicians Total Care, Inc.2011-05-17Not applicableUs
CalcitriolSolution1 ug/1mLOralWest-Ward Pharmaceuticals Corp.2003-07-18Not applicableUs
CalcitriolCapsule0.25 ug/1OralAtlantic Biologicals Corps.2014-12-12Not applicableUs
CalcitriolCapsule, liquid filled0.25 ug/1OralTeva2001-10-152017-07-31Us0093 065720180814 13942 5napw9
CalcitriolCapsule0.5 ug/1Oralbryant ranch prepack2014-12-12Not applicableUs
CalcitriolCapsule0.5 ug/1OralHeritage2018-05-29Not applicableUs
CalcitriolCapsule, liquid filled0.25 ug/1OralPhysicians Total Care, Inc.2005-12-02Not applicableUs54868 458420180907 15195 ya14be
CalcitriolCapsule, liquid filled0.25 ug/1OralNucare Pharmaceuticals,inc.2013-05-29Not applicableUs
CalcitriolCapsule, liquid filled0.5 ug/1OralTeva Pharmaceuticals USA, Inc.2016-07-01Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ValidermCalcitriol (0.2 mg/0.2mg) + Fluticasone propionate (0.05 g/0.05g) + Tacrolimus hydrate (0.05 g/0.05g)KitAccumix Pharmaceuticals2014-12-152015-07-17Us
International/Other Brands
Asentar / Calcitriol Oral Solution (Roxane) / Decostriol (Mibe Jena (Germany), Jesalis (Hong Kong, Thailand))
Categories
UNII
FXC9231JVH
CAS number
32222-06-3
Weight
Average: 416.6365
Monoisotopic: 416.329045274
Chemical Formula
C27H44O3
InChI Key
GMRQFYUYWCNGIN-NKMMMXOESA-N
InChI
InChI=1S/C27H44O3/c1-18(8-6-14-26(3,4)30)23-12-13-24-20(9-7-15-27(23,24)5)10-11-21-16-22(28)17-25(29)19(21)2/h10-11,18,22-25,28-30H,2,6-9,12-17H2,1,3-5H3/b20-10+,21-11-/t18-,22-,23-,24+,25+,27-/m1/s1
IUPAC Name
(1R,3S,5Z)-5-{2-[(1R,3aS,4E,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol
SMILES
C[C@H](CCCC(C)(C)O)[C@@]1([H])CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C

Pharmacology

Indication

Used to treat vitamin D deficiency or insufficiency, refractory rickets (vitamin D resistant rickets), familial hypophosphatemia and hypoparathyroidism, and in the management of hypocalcemia and renal osteodystrophy in patients with chronic renal failure undergoing dialysis. Also used in conjunction with calcium in the management and prevention of primary or corticosteroid-induced osteoporosis.

Associated Conditions
Pharmacodynamics

Calcitriol, a pharmaceutical form of vitamin D, has anti-osteoporotic, immunomodulatory, anticarcinogenic, antipsoriatic, antioxidant, and mood-modulatory activities. Calcitriol has been found to be effective in the treatment of psoriasis when applied topically. Calcitriol has been found to induce differentiation and/or inhibit cell proliferation in a number of malignant cell lines including human prostate cancer cells. Vitamin D deficiency has long been suspected to increase the susceptibility to tuberculosis. The active form of calcitriol, 1,25-(OH)2-D3, has been found to enhance the ability of mononuclear phagocytes to suppress the intracellular growth of Mycobacterium tuberculosis. 1,25-(OH)2-D3 has demonstrated beneficial effects in animal models of such autoimmune diseases as rheumatoid arthritis. It has also been found to induce monocyte differentiation and to inhibit lymphocyte proliferation and production of cytokines, including interleukin IL-1 and IL-2, as well as to suppress immunoglobulin secretion by B lymphocytes. Vitamin D appears to demonstrate both immune-enhancing and immunosuppressive effects.

Mechanism of action

The mechanism of action of calcitriol in the treatment of psoriasis is accounted for by their antiproliferative activity for keratinocytes and their stimulation of epidermal cell differentiation. The anticarcinogenic activity of the active form of Calcitriol appears to be correlated with cellular vitamin D receptor (VDR) levels. Vitamin D receptors belong to the superfamily of steroid-hormone zinc-finger receptors. VDRs selectively bind 1,25-(OH)2-D3 and retinoic acid X receptor (RXR) to form a heterodimeric complex that interacts with specific DNA sequences known as vitamin D-responsive elements. VDRs are ligand-activated transcription factors. The receptors activate or repress the transcription of target genes upon binding their respective ligands. It is thought that the anticarcinogenic effect of Calcitriol is mediated via VDRs in cancer cells. The immunomodulatory activity of calcitriol is thought to be mediated by vitamin D receptors (VDRs) which are expressed constitutively in monocytes but induced upon activation of T and B lymphocytes. 1,25-(OH)2-D3 has also been found to enhance the activity of some vitamin D-receptor positive immune cells and to enhance the sensitivity of certain target cells to various cytokines secreted by immune cells.

TargetActionsOrganism
AVitamin D3 receptor
antagonist
Human
UHomeobox protein Hox-A10Not AvailableHuman
UVitamin D-binding proteinNot AvailableHuman
Absorption

Rapidly absorbed from the intestine.

Volume of distribution
Not Available
Protein binding

99.9%

Metabolism

The first pathway involves 24-hydroxylase activity in the kidney; this enzyme is also present in many target tissues which possess the vitamin D receptor such as the intestine. The end product of this pathway is a side chain shortened metabolite, calcitroic acid. The second pathway involves the conversion of calcitriol via the stepwise hydroxylation of carbon-26 and carbon-23, and cyclization to yield ultimately 1a,25R(OH)2-26,23S-lactone D3. The lactone appears to be the major metabolite circulating in humans.

Route of elimination

Enterohepatic recycling and biliary excretion of calcitriol occur. The metabolites of calcitriol are excreted primarily in feces. Cumulative excretion of radioactivity on the sixth day following intravenous administration of radiolabeled calcitriol averaged 16% in urine and 49% in feces.

Half life

5-8 hours

Clearance
  • 15.3 mL/hr/kg [pediatric patients (age range: 1.8 to 16 years) undergoing peritoneal dialysis receiving dose of 10.2 ng/kg (SD 5.5 ng/kg) for 2 months]
Toxicity

LD50 (oral, rat) = 620 μg/kg; LD50 (intraperitoneal, rat) > 5 mg/kg; Overdose evident in elevated blood calcium levels causing symptoms of anorexia, nausea and vomiting, polyuria, polydipsia, weakness, pruritus, and nervousness, potentially with irreversible calcification of soft tissue in the kidney and liver.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Calcitriol.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Calcitriol.
1alpha-Hydroxyvitamin D5The risk or severity of adverse effects can be increased when Calcitriol is combined with 1alpha-Hydroxyvitamin D5.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Calcitriol.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Calcitriol.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Calcitriol.
6-Deoxyerythronolide BThe metabolism of Calcitriol can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Calcitriol.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Calcitriol.
AbirateroneThe metabolism of Abiraterone can be increased when combined with Calcitriol.
Food Interactions
Not Available

References

Synthesis Reference

Raymond E. Conrow, "Process for preparation of calcitriol lactone and related intermediates." U.S. Patent US5457245, issued April, 1994.

US5457245
General References
  1. Brawer MK: Recent Progress in the Treatment of Advanced Prostate Cancer With Intermittent Dose-Intense Calcitriol (DN-101). Rev Urol. 2007 Winter;9(1):1-8. [PubMed:17396166]
  2. Beer TM, Javle M, Lam GN, Henner WD, Wong A, Trump DL: Pharmacokinetics and tolerability of a single dose of DN-101, a new formulation of calcitriol, in patients with cancer. Clin Cancer Res. 2005 Nov 1;11(21):7794-9. [PubMed:16278401]
External Links
Human Metabolome Database
HMDB0001903
KEGG Drug
D00129
KEGG Compound
C01673
PubChem Compound
5280453
PubChem Substance
46508162
ChemSpider
4444108
BindingDB
50200182
ChEBI
17823
ChEMBL
CHEMBL846
Therapeutic Targets Database
DAP000289
PharmGKB
PA448717
IUPHAR
2779
Guide to Pharmacology
GtP Drug Page
HET
VDX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Calcitriol
ATC Codes
A11CC04 — CalcitriolD05AX03 — Calcitriol
AHFS Codes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
  • 88:16.00 — Vitamin D
PDB Entries
1db1 / 1ie9 / 1rk3 / 2hc4 / 2zbz / 2zlc / 3cv9 / 3m7r / 3vt3 / 3vt7
show 2 more
FDA label
Download (39.2 KB)
MSDS
Download (74.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedNot AvailableAnemia of Chronic Disease / Chronic Kidney Disease (CKD)1
0Not Yet RecruitingTreatmentPostmenopausal Osteoporoses1
0TerminatedTreatmentDeficiency, Vitamin D / High Blood Pressure (Hypertension)1
1Active Not RecruitingPreventionCancer of the Ovary / Cancer, Breast / Cervical Cancers / Endometrial Cancers / Malignancies / Primary Peritoneal Carcinoma / Sarcoma, Bone / Tumors, Solid1
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailablePostmenopausal Osteoporosis, Multiple Sites / To Study the Safety and Tolerability of 2MD in Postmenopausal Women, the Intended Target Population1
1CompletedPreventionAdenocarcinomas / Colorectal Adenomas / Colorectal Polyps1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentPsoriasis / Psoriasis Vulgaris (Plaque Psoriasis)1
1, 2CompletedBasic ScienceMouth Neoplasms1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2CompletedTreatmentObstructive Sleep Apnea (OSA)1
1, 2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingPreventionBone Loss / Calcifications, Vascular / End Stage Renal Disease (ESRD) / Fracture Bone / Transplantation, Kidney1
2Active Not RecruitingPreventionCancer, Breast1
2Active Not RecruitingTreatmentKlinefelter's Syndrome / Male Infertility / Y-chromosome Microdeletions1
2CompletedNot AvailableDiabetes, Diabetes Mellitus Type 11
2CompletedPreventionBone and Bones / Neoplasms, Breast1
2CompletedPreventionDiabetes, Diabetes Mellitus Type 11
2CompletedTreatmentBasal Cell Carcinoma (BCC)1
2CompletedTreatmentChronic Plaque Psoriasis1
2CompletedTreatmentEnd Stage Renal Disease (ESRD) / Renal Osteodystrophy1
2CompletedTreatmentHyperparathyroidism, Secondary / Renal Osteodystrophy1
2CompletedTreatmentMyelodysplastic Syndromes1
2CompletedTreatmentPsoriasis1
2CompletedTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
2CompletedTreatmentSevere Sepsis or Septic Shock1
2CompletedTreatmentParathyroid deficiency1
2RecruitingPreventionAcute Kidney Injury (AKI) / Critically-ill Patients1
2SuspendedTreatmentMalignant Neoplasm of Pancreas1
2TerminatedTreatmentCastration-Resistant Prostate Cancer (CRPC)1
2TerminatedTreatmentHypocalcemia1
2TerminatedTreatmentHypocalcemia / Hypovitaminosis D1
2TerminatedTreatmentProstate Cancer / Prostatic Neoplasms1
2Unknown StatusTreatmentAdvanced Intrahepatic Cholangiocarcinoma1
2Unknown StatusTreatmentMyelodysplastic Syndrome1
2Unknown StatusTreatmentSystemic Lupus Erythematosus (SLE)1
2, 3Unknown StatusTreatmentProstate Cancer1
3CompletedPreventionCardiac Transplantation / Osteoporosis1
3CompletedTreatmentArterial Dysfunction / Chronic Kidney Disease (CKD)1
3CompletedTreatmentChronic Kidney Disease (CKD) / Deficiency, Vitamin D / Hyperparathyroidism, Secondary1
3CompletedTreatmentFacial Angiofibroma1
3CompletedTreatmentOsteopetrosis1
3RecruitingTreatmentDiabetic Nephropathies1
3RecruitingTreatmentSecondary Hyperparathyroidism-Chronic Kidney Disease1
3TerminatedTreatmentProstate Cancer1
4Active Not RecruitingTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
4CompletedPreventionChronic Kidney Disease (CKD) / Coronary Calcification / Deficiency, Vitamin D / Disorders of Calcium and Bone Metabolism1
4CompletedTreatmentAnemias / Chronic Kidney Disease (CKD)1
4CompletedTreatmentCardiorenal Syndrome / Chronic Allograft Nephropathy (CAN)1
4CompletedTreatmentChronic Kidney Disease (CKD) / Hyperparathyroidism, Secondary2
4CompletedTreatmentDeficiency, Vitamin D1
4CompletedTreatmentEnd Stage Renal Disease (ESRD) / Hyperparathyroidism, Secondary1
4CompletedTreatmentIgA Nephropathy1
4CompletedTreatmentPityriasis Alba1
4CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
4CompletedTreatmentStage 3 Chronic Kidney Disease1
4Enrolling by InvitationSupportive CareMalignancies1
4Not Yet RecruitingPreventionChronic Kidney Disease Stage 1 / Chronic Kidney Disease Stage 21
4RecruitingTreatmentInfertilities1
4TerminatedTreatmentDialysis therapy / Hyperparathyroidism, Secondary1
4TerminatedTreatmentEnd-Stage Kidney Disease1
4TerminatedTreatmentHypercalcemia / Hyperparathyroidism, Secondary / Hyperphosphataemia / Renal Failure1
4Unknown StatusScreeningDiabetic Nephropathies1
4Unknown StatusTreatmentAsthma Bronchial1
4Unknown StatusTreatmentAutoimmune Diseases / Glomerulonephritis1
4Unknown StatusTreatmentChronic Kidney Disease (CKD) / Proteinuria1
4Unknown StatusTreatmentOsteoporosis1
4Unknown StatusTreatmentProteinuria1
4WithdrawnTreatmentNephritis / Proteinuria / Systemic Lupus Erythematosus (SLE)1
Not AvailableCompletedPreventionBMI >30 kg/m2 / Type 2 Diabetes Mellitus1
Not AvailableCompletedPreventionLung Cancers / Precancerous Conditions / Tobacco Use Disorders1
Not AvailableCompletedTreatmentCrohn's Disease (CD) / Rheumatoid Arthritis1
Not AvailableCompletedTreatmentHIV Seropositive1
Not AvailableCompletedTreatmentHyperparathyroidism, Secondary / Hypocalcemia1
Not AvailableCompletedTreatmentHyperparathyroidism / Kidney Diseases1
Not AvailableCompletedTreatmentIgA Nephropathy1
Not AvailableCompletedTreatmentPsoriasis1
Not AvailableTerminatedNot AvailableEnd-Stage Renal Disease (ESRD) / Hyperparathyroidism, Secondary1
Not AvailableUnknown StatusNot AvailableNeoplasms, Breast / Postmenopausal Disorder1
Not AvailableUnknown StatusTreatmentProstatic Neoplasms1
Not AvailableWithdrawnTreatmentChronic Kidney Disease (CKD) / Deficiency, Vitamin D1
Not AvailableWithdrawnTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableWithdrawnTreatmentPsoriasis1

Pharmacoeconomics

Manufacturers
  • Roxane laboratories inc
  • Teva pharmaceuticals usa inc
  • Validus pharmaceuticals llc
  • Abbott laboratories hosp products div
  • Akorn inc
  • App pharmaceuticals llc
  • Fresenius medical care north america
  • Genix therapeutics inc
  • Hospira inc
  • Luitpold pharmaceuticals inc
  • Lyne laboratories inc
  • Teva parenteral medicines inc
  • Galderma laboratories lp
Packagers
  • Abbott Laboratories Ltd.
  • Akorn Inc.
  • American Regent
  • APP Pharmaceuticals
  • Atlantic Biologicals Corporation
  • Cardinal Health
  • Catalent Pharma Solutions
  • DSM Corp.
  • F Hoffmann-La Roche Ltd.
  • Galderma Laboratories
  • Gulf Pharmaceutical Industries
  • Hospira Inc.
  • Kaiser Foundation Hospital
  • Luitpold Pharmaceuticals Inc.
  • Nephrx LLC
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Pierre Fabre
  • Ranbaxy Laboratories
  • Resource Optimization and Innovation LLC
  • Roxane Labs
  • Teva Pharmaceutical Industries Ltd.
  • Tya Pharmaceuticals
  • Validus Pharmaceuticals
Dosage forms
FormRouteStrength
SolutionIntravenous2 mcg
CapsuleOral0.25 ug/1
CapsuleOral0.5 ug/1
Capsule, liquid filledOral0.50 ug/1
InjectionIntravenous1 ug/1mL
InjectionIntravenous2 ug/1mL
Injection, solutionIntravenous1 mg/1mL
Injection, solutionIntravenous1 ug/1mL
Injection, solutionIntravenous2 ug/1mL
OintmentTopical3 ug/1g
SolutionIntravenous1 ug/1mL
SolutionIntravenous1 mcg
Capsule, gelatin coatedOral0.25 ug/1
Capsule, gelatin coatedOral0.5 ug/1
Capsule, liquid filledOral0.25 ug/1
Capsule, liquid filledOral0.5 ug/1
SolutionOral1 ug/1mL
CapsuleOral0.25 mcg
CapsuleOral0.5 mcg
SolutionOral1 mcg
OintmentTopical3 mcg
Kit
Prices
Unit descriptionCostUnit
Calcijex 2 mcg/ml19.38USD ml
Calcijex 1 mcg/ml ampul14.7USD ml
Calcijex 1 mcg/ml10.68USD ml
Calcitriol 1 mcg/ml ampul6.0USD ml
Vectical 3 mcg/g ointment4.68USD g
Rocaltrol 0.5 mcg capsule2.02USD capsule
Calcitriol 0.5 mcg capsule1.97USD capsule
Rocaltrol 0.25 mcg capsule1.46USD capsule
Calcitriol 0.25 mcg capsule1.45USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6265392Yes2000-02-022020-02-02Us
US6051567Yes2000-02-022020-02-02Us
US6274169Yes2000-02-022020-02-02Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)113-114Uskokovic, M.R., Narwid, T.A., lacobelli, J.A. and Baggiolini, E.; U.S. Patent 3,993,675; November 23, 1976; assigned to Hoffmann-La Roche, Inc.
water solubilityInsolubleNot Available
logP5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00667 mg/mLALOGPS
logP5.51ALOGPS
logP4.35ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)14.39ChemAxon
pKa (Strongest Basic)-1.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area60.69 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity126.53 m3·mol-1ChemAxon
Polarizability51.02 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9924
Blood Brain Barrier+0.8524
Caco-2 permeable+0.7812
P-glycoprotein substrateSubstrate0.7843
P-glycoprotein inhibitor INon-inhibitor0.6065
P-glycoprotein inhibitor IINon-inhibitor0.6073
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateNon-substrate0.8367
CYP450 2D6 substrateNon-substrate0.9022
CYP450 3A4 substrateSubstrate0.7506
CYP450 1A2 substrateNon-inhibitor0.9033
CYP450 2C9 inhibitorNon-inhibitor0.8354
CYP450 2D6 inhibitorNon-inhibitor0.9495
CYP450 2C19 inhibitorNon-inhibitor0.7796
CYP450 3A4 inhibitorNon-inhibitor0.813
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6175
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9274
BiodegradationNot ready biodegradable0.9937
Rat acute toxicity5.1352 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8734
hERG inhibition (predictor II)Non-inhibitor0.8579
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 / Tertiary alcohols / Secondary alcohols / Cyclic alcohols and derivatives / Hydrocarbon derivatives
Substituents
Triterpenoid / Tertiary alcohol / Cyclic alcohol / Secondary alcohol / Organic oxygen compound / Hydrocarbon derivative / Organooxygen compound / Alcohol / Aliphatic homopolycyclic compound
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
triol, D3 vitamins, hydroxycalciol (CHEBI:17823) / Steroid hormones (C01673) / Vitamin D3 and derivatives (LMST03020258)

Targets

Details
1. Vitamin D3 receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds to the DNA sequence 5'-AA[AT]TTTTATTAC-3'.
Specific Function
Histone deacetylase binding
Gene Name
HOXA10
Uniprot ID
P31260
Uniprot Name
Homeobox protein Hox-A10
Molecular Weight
42413.825 Da
References
  1. Du H, Daftary GS, Lalwani SI, Taylor HS: Direct regulation of HOXA10 by 1,25-(OH)2D3 in human myelomonocytic cells and human endometrial stromal cells. Mol Endocrinol. 2005 Sep;19(9):2222-33. Epub 2005 May 19. [PubMed:15905361]
Details
3. Vitamin D-binding protein
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Arnaud J, Constans J: Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet. 1993 Sep;92(2):183-8. [PubMed:8370586]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Oxidoreductase activity
Specific Function
Has a role in maintaining calcium homeostasis. Catalyzes the NADPH-dependent 24-hydroxylation of calcidiol (25-hydroxyvitamin D(3)) and calcitriol (1-alpha,25-dihydroxyvitamin D(3)). The enzyme can...
Gene Name
CYP24A1
Uniprot ID
Q07973
Uniprot Name
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
Molecular Weight
58874.695 Da
References
  1. Schuster I: Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta. 2011 Jan;1814(1):186-99. doi: 10.1016/j.bbapap.2010.06.022. Epub 2010 Jul 7. [PubMed:20619365]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Xu Y, Hashizume T, Shuhart MC, Davis CL, Nelson WL, Sakaki T, Kalhorn TF, Watkins PB, Schuetz EG, Thummel KE: Intestinal and hepatic CYP3A4 catalyze hydroxylation of 1alpha,25-dihydroxyvitamin D(3): implications for drug-induced osteomalacia. Mol Pharmacol. 2006 Jan;69(1):56-65. Epub 2005 Oct 5. [PubMed:16207822]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:39