Calcitriol
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Basic Info
| Common Name | Calcitriol(F04730) |
| 2D Structure | |
| Description | Calcitriol or 1,25-dihydroxycholecalciferol (abbreviated 1,25-(OH)<sub>2</sub>-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 (PO<sub>4</sub><sup>3-</sup>) 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. |
| FRCD ID | F04730 |
| CAS Number | 32222-06-3 |
| PubChem CID | 5280453 |
| Formula | C27H44O3 |
| IUPAC Name | (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol |
| 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 |
| Canonical SMILES | CC(CCCC(C)(C)O)C1CCC2C1(CCCC2=CC=C3CC(CC(C3=C)O)O)C |
| Isomeric SMILES | C[C@H](CCCC(C)(C)O)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@H](C[C@@H](C3=C)O)O)C |
| Wikipedia | Calcitriol |
| Synonyms |
calcitriol
1alpha,25-Dihydroxycholecalciferol
32222-06-3
Rocaltrol
Calcijex
Topitriol
1alpha,25-Dihydroxyvitamin D3
Silkis
Soltriol
Calcitriolum
|
| Classifies |
Predicted: Pollutant
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Lipids and lipid-like molecules |
| Class | Steroids and steroid derivatives |
| Subclass | Vitamin D and derivatives |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Vitamin D and derivatives |
| Alternative Parents | |
| Molecular Framework | Aliphatic homopolycyclic compounds |
| Substituents | Triterpenoid - Tertiary alcohol - Cyclic alcohol - Secondary alcohol - Organic oxygen compound - Hydrocarbon derivative - Organooxygen compound - Alcohol - Aliphatic homopolycyclic compound |
| 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 416.646 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 6 |
| Complexity | 688 |
| Monoisotopic Mass | 416.329 |
| Exact Mass | 416.329 |
| XLogP | 5.1 |
| Formal Charge | 0 |
| Heavy Atom Count | 30 |
| Defined Atom Stereocenter Count | 6 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 2 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.8524 |
| Human Intestinal Absorption | HIA+ | 0.9924 |
| Caco-2 Permeability | Caco2+ | 0.7812 |
| P-glycoprotein Substrate | Substrate | 0.7843 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.6065 |
| Non-inhibitor | 0.6073 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8178 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.5400 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8367 |
| CYP450 2D6 Substrate | Non-substrate | 0.9022 |
| CYP450 3A4 Substrate | Substrate | 0.7506 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9033 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8354 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9495 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7796 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8130 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.6175 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.8734 |
| Non-inhibitor | 0.8579 | |
| AMES Toxicity | Non AMES toxic | 0.9133 |
| Carcinogens | Non-carcinogens | 0.9274 |
| Fish Toxicity | High FHMT | 0.9945 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9861 |
| Honey Bee Toxicity | High HBT | 0.8559 |
| Biodegradation | Not ready biodegradable | 0.9937 |
| Acute Oral Toxicity | I | 0.8580 |
| Carcinogenicity (Three-class) | Non-required | 0.6277 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.9842 | LogS |
| Caco-2 Permeability | 1.1589 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 5.1352 | LD50, mol/kg |
| Fish Toxicity | 0.3268 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.9964 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| [Disturbances of calcium metabolism and vitamin D supplementation in sarcoidosis - two-way street]. | Pol Merkur Lekarski | 2018 Mar 27 | 29601566 |
| Effects of Vitamin D Supplementation on Semen Quality, Reproductive Hormones, andLive Birth Rate: A Randomized Clinical Trial. | J Clin Endocrinol Metab | 2018 Mar 1 | 29126319 |
| PTH(1-34) for Surgical Hypoparathyroidism: A 2-Year Prospective, Open-LabelInvestigation of Efficacy and Quality of Life. | J Clin Endocrinol Metab | 2018 Jan 1 | 29099939 |
| Vitamin D deficiency causes rickets in an urban informal settlement in Kenya and is associated with malnutrition. | Matern Child Nutr | 2018 Jan | 28470840 |
| Experimental study on 1,25(OH)<sub>2</sub> D<sub>3</sub> amelioration of oral lichen planus through regulating NF-κB signaling pathway. | Oral Dis | 2017 Sep | 28231625 |
| Current concepts regarding calcium metabolism and bone health in sarcoidosis. | Curr Opin Pulm Med | 2017 Sep | 28598871 |
| Safety and Efficacy of Recombinant Human Parathyroid Hormone in Adults WithHypoparathyroidism Randomly Assigned to Receive Fixed 25-μg or 50-μg Daily Doses. | Clin Ther | 2017 Oct | 28942334 |
| Role of Vitamin D in Maintaining Renal Epithelial Barrier Function in Uremic Conditions. | Int J Mol Sci | 2017 Nov 26 | 29186865 |
| Vitamin D3 repressed astrocyte activation following lipopolysaccharide stimulation in vitro and in neonatal rats. | Neuroreport | 2017 Jun 14 | 28430709 |
| Use of calcitriol to maintain postpartum blood calcium and improve immunefunction in dairy cows. | J Dairy Sci | 2017 Jul | 28501403 |
| Effect of daily calcitriol supplementation with and without calcium on diseaseregression in non-alcoholic fatty liver patients following an energy-restricteddiet: Randomized, controlled, double-blind trial. | Clin Nutr | 2017 Dec | 27720403 |
| Effect of additive calcium administration on FGF23 levels in patients with mildchronic kidney disease treated with calcitriol: a randomized, open-labeledclinical trial. | Ther Clin Risk Manag | 2017 Aug 14 | 28860784 |
| Hypothalamic Vitamin D Improves Glucose Homeostasis and Reduces Weight. | Diabetes | 2016 Sep | 27217488 |
| 1,25 Dihydroxyvitamin D circulating levels, calcitriol administration, andincidence of acute rejection, CMV infection, and polyoma virus infection in renaltransplant recipients. | Clin Transplant | 2016 Oct | 27532453 |
| Vitamin D receptor signaling improves Hutchinson-Gilford progeria syndrome cellular phenotypes. | Oncotarget | 2016 May 24 | 27145372 |
| Cinacalcet as adjunctive therapy in pseudohypoparathyroidism type 1b. | Pediatr Nephrol | 2016 May | 26628282 |
| How well are the optimal serum 25OHD concentrations reached in high-doseintermittent vitamin D therapy? a placebo-controlled study on comparison between 100 000 IU and 200 000 IU of oral D3 every 3 months in elderly women. | Clin Endocrinol (Oxf) | 2016 Jun | 26725707 |
| Therapy of Hypoparathyroidism With PTH(1-84): A Prospective Six YearInvestigation of Efficacy and Safety. | J Clin Endocrinol Metab | 2016 Jul | 27144931 |
| Impact of preoperative Vitamin D3 administration on postoperative hypocalcaemiain patients undergoing total thyroidectomy (HypoCalViD): study protocol for arandomized controlled trial. | Trials | 2016 Feb 20 | 26899387 |
| Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin DMetabolites in the Blood of Healthy Adult Cats. | PLoS One | 2016 Feb 12 | 26870965 |
Targets
- General Function:
- Iron ion binding
- Specific Function:
- Catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D) to 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D) plays an important role in normal bone growth, calcium metabolism, and tissue differentiation.
- Gene Name:
- CYP27B1
- Uniprot ID:
- O15528
- Molecular Weight:
- 56503.475 Da
- 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)2D 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)2D 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.
References
- Maehr H, Uskokovic MR, Reddy GS, Adorini L: Calcitriol derivatives with two different side chains at C-20. 24-hydroxy derivatives as metabolic products and molecular probes for VDR exploration. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):35-8. [15225743 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
- Gene Name:
- AR
- Uniprot ID:
- P10275
- Molecular Weight:
- 98987.9 Da
References
- Nakamura M, Makishima M, Hashimoto Y: Development of silicon-containing bis-phenol derivatives as androgen receptor antagonists: selectivity switching by C/Si exchange. Bioorg Med Chem. 2013 Apr 1;21(7):1643-51. doi: 10.1016/j.bmc.2013.01.060. Epub 2013 Feb 6. [23462715 ]
- 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
- Molecular Weight:
- 52963.025 Da
References
- Sanchez-Abella L, Fernandez S, Verstuyf A, Verlinden L, Gotor V, Ferrero M: Synthesis, conformational analysis, and biological evaluation of 19-nor-vitamin D3 analogues with A-ring modifications. J Med Chem. 2009 Oct 8;52(19):6158-62. doi: 10.1021/jm900711d. [19739672 ]
- 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
- 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)2D 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)2D 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.
References
- Reinhart GA: Vitamin D analogs: novel therapeutic agents for cardiovascular disease? Curr Opin Investig Drugs. 2004 Sep;5(9):947-51. [15503649 ]