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Purity: ≥98%
Calcitriol (RO215535, Topitriol; 1,25(OH)2D3) is an agonist of the vitamin D receptor (VDR) and the form of vitamin D that is metabolically and hormonally active. When calcitriol is converted, it produces metabolites that are more powerful and act faster than other vitamin D forms. Calcitriol regulates the differentiation, growth, and function of the cell immune system, which plays a major role in maintaining mineral and skeletal homeostasis. Studies conducted in vitro have revealed that calcitriol can inhibit the production of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in human peripheral blood cells (PBMC) stimulated by lipopolysaccharide (LPS) in a dose-dependent manner.
| Targets |
Human Endogenous Metabolite; VDR/vitamin D receptor
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| ln Vitro |
Calcitriol is a potent inhibitor of PHA-induced lymphocyte proliferation, achieving 70% suppression of tritiated thymidine incorporation after 72 hours in culture. In a concentration-dependent manner, calcitriol reduces the production of interleukin-2 (IL-2) by PHA-stimulated peripheral blood mononuclear cells.[1]
Calcitriol increases the intracellular calcium concentration ([Ca2+]i) in less than 5 seconds by causing the endoplasmic reticulum to release calcium and forming inositol 1,4, 5-trisphosphate and diacylglycerol.[2] Calcitriol can both stimulate and prevent the growth of human prostate adenocarcinoma cells. Type IV collagenases' (MMP-2 and MMP-9) secreted levels are selectively decreased by calcitriol.[3] Calcitriol increases the antitumor activity of platinum-based drugs and exhibits antiproliferative activity in prostatic adenocarcinoma and squamous cell carcinoma. In PC-3 and murine squamous cell carcinoma cells, calcitriol prior to paclitaxel significantly lowers clonogenic survival compared with either agent alone.[4] Calcitriol is a potent anti-proliferative agent that targets a broad range of cancerous cell types. Growth factor receptor expression is modulated, apoptosis and differentiation are induced, and G0/G1 arrest is increased in response to calcitriol. Calcitriol inhibits the motility and invasiveness of tumor cells as well as the development of new blood vessels, thereby amplifying the antitumor effects of numerous cytotoxic agents.[5] |
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| ln Vivo |
Calcitriol treatment (150 ng/kg per day for 4.5 months) improves relaxations (pD2: 6.30±0.09, Emax: 68.6±3.9% in OVX treated with Calcitriol, n=8). Both kidneys of OVX rats have decreased renal blood flow, which is remedied by calcitriol treatment. Chronic calcitriol administration decreases the increased expression of Thromboxane-prostanoid (TP) receptor and COX-2 in the renal arteries of OVX rats[3]. Treatment with high- and low-dose calcitriol reduces the fructose-fed rats' systolic blood pressure (SBP) by 14±4 and 9±4 mmHg, respectively, on day 56. When compared to other groups, high-dose calcitriol treatment (20 ng/kg per day) significantly raises serum ionized calcium levels (1.44±0.05 mmol/L).
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| Enzyme Assay |
Recent studies have suggested that vitamin D may have other important biologic activities in addition to its well-characterized role in the maintenance of calcium homeostasis. Discovery of cytosolic receptors for vitamin D in human peripheral blood monocytes and lectin-stimulated lymphocytes prompted us to study the effects of 1,25-dihydroxyvitamin D3 (calcitriol), the most biologically active metabolite of vitamin D, upon phytohemagglutinin (PHA)-induced lymphocyte blast transformation. We have found that calcitriol is a potent inhibitor of PHA-induced lymphocyte proliferation, achieving 70% inhibition of tritiated thymidine incorporation after 72 h in culture. Furthermore, calcitriol suppressed interleukin-2 (IL-2) production by PHA-stimulated peripheral blood mononuclear cells in a concentration-dependent fashion. Lastly, the suppressive effect of calcitriol on cellular proliferation was partially reversed by the addition of saturating amounts of purified IL-2. We conclude that calcitriol is a potent inhibitor of PHA-induced lymphocyte blast transformation and that this effect is mediated, in part, through suppression of IL-2 production. Thus, calcitriol appears to possess immunoregulatory properties that have been unappreciated heretofore[1].
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| Cell Assay |
Calcitriol (100 nM) or DMSO (vehicle control) were used to treat CLL cells. At the designated time intervals, cells were harvested with a light trypsinization.
The effect of treatment on growth of the murine squamous cell carcinoma (SCCVII/SF) and human prostatic adenocarcinoma (PC-3) was determined by clonogenic assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and monitoring tumor growth. Treatment of SCC or PC-3 cells in vitro with calcitriol prior to paclitaxel significantly reduced clonogenic survival compared with either agent alone. Median-dose effect analysis revealed that calcitriol and paclitaxel interact synergistically[4]. |
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| Additional Infomation |
Calcitriol is a hydroxycalciol that is calcidiol in which the pro-S hydrogen of calcidiol is replaced by a hydroxy group. It is the active form of vitamin D3, produced fom calciol via hydoxylation in the liver to form calcidiol, which is subsequently oxidised in the kidney to give calcitriol. It has a role as a bone density conservation agent, an antipsoriatic, an immunomodulator, an antineoplastic agent, a calcium channel modulator, a nutraceutical, a calcium channel agonist, a metabolite, a hormone, a human metabolite and a mouse metabolite. It is a hydroxycalciol, a member of D3 vitamins and a triol.
View MoreCalcitriol is an active metabolite of vitamin D with 3 hydroxyl (OH) groups and is commonly referred to as 1,25-dihydroxycholecalciferol, or 1alpha,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D3. It is produced in the body after series of conversion steps of 7-dehydrocholesterol from exposure to UV light. 7-dehydrocholesterol is converted to [DB00169] (vitamin D3) in the skin, which is then converted to [DB00146] in the liver and kidneys. [DB00146] undergoes hydroxylation to form calcitriol via 1α-hydroxylase (CYP27B1) activity. Calcitriol is considered to be the most potent metabolite of vitamin D in humans. Renal production of calcitriol is stimulated in response to PTH, low calcium and low phosphate. Calcitriol plays a role in plasma calcium regulation in concert with parathyroid hormone (PTH) by enhancing absorption of dietary calcium and phosphate from the gastrointestinal tract, promoting renal tubular reabsorption of calcium in the kidneys, and stimulating the release of calcium stores from the skeletal system. In addition to promoting fatty acid synthesis and inhibiting lipolysis, calcitriol has been demonstrated to increase energy efficiency by suppressing UCP2 expression, which is modulated by signaling pathways of classical nuclear receptors (nVDR), where calcitriol acts as a natural ligand. There is also evidence that calcitriol modulates the action of cytokines and may regulate immune and inflammatory response, cell turnover, cell differentiation. Administered orally and intravenously, calcitriol is commonly used as a medication in the treatment of secondary hyperparathyroidism and resultant metabolic bone disease, hypocalcemia in patients undergoing chronic renal dialysis, and osteoporosis. It is also available in topical form for the treatment of mild to moderate plaque psoriasis in adults. Calcitriol is marketed under various trade names including Rocaltrol (Roche), Calcijex (Abbott) and Decostriol (Mibe, Jesalis). Calcitriol is a natural product found in Solanum glaucophyllum, Homo sapiens, and Trypanosoma brucei with data available. Calcitriol is a synthetic physiologically-active analog of vitamin D, specifically the vitamin D3 form. Calcitriol regulates calcium in vivo by promoting absorption in the intestine, reabsorption in the kidneys, and, along with parathyroid hormone, regulation of bone growth. A calcitriol receptor-binding protein appears to exist in the mucosa of human intestine. Calcitriol also induces cell cycle arrest at G0/G1 phase of the cell cycle, cell differentiation, and apoptosis, resulting in inhibition of proliferation of some tumor cell types. This agent may be chemopreventive for colon and prostate cancers. (NCI04) 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. The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. Calcitriol is a biologically active calcitrophic hormone with anti-osteoporotic, immunomodulatory, anticarcinogenic, antipsoriatic, antioxidant, and mood-modulatory activities. Its main sites of action are the intestine, bone, kidney and parathyroid hormone. Calcitriol is a ligand for the vitamin D nuclear receptor, which is expressed in, but not limited to, gastrointestinal (GI) tissues, bones, and kidneys. As an active form of vitamin D3, calcitriol elevates the plasma levels of calcium by stimulating intestinal calcium uptake, increasing reabsorption of calcium by the kidneys, and possibly increasing the release of calcium from skeletal stores. The duration of pharmacologic activity of a single dose of exogenous calcitriol is expected to be about 3 to 5 days. In addition to its important role in calcium metabolism, other pharmacological effects of calcitriol have been studied in various conditions including cancer models. Various studies demonstrated expression of vitamin D receptors in cancer cell lines, including mouse myeloid leukemia cells. Calcitriol has been found to induce differentiation and/or inhibit cell proliferation _in vitro_ and _in vivo_ in many cell types, such as malignant cell lines carcinomas of the breast, prostate, colon, skin, and brain, myeloid leukemia cells, and others. In early human prostate cancer trials, administration of 1.5 µg/d calcitriol in male participants resulted in a reduction in the rate of PSA rise in most participants, however it was coincided with dose-limiting hypercalcemia in most participants. Hypercalcemia and hypercalcuria were evident in numerous initial trials, and this may be due to these trials not testing the drug at concentrations that are active in preclinical systems. Findings from preclinical data show an additive or synergistic antineoplastic action of calcitriol when combined with agents including dexamethasone, retinoids, and radiation, as well as several cytotoxic chemotherapy drugs such as platinum compounds. 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. Vitamin D appears to demonstrate both immune-enhancing and immunosuppressive effects. Reference: https://pubchem.ncbi.nlm.nih.gov/compound/5280453 |
| Molecular Formula |
C27H44O3
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| Molecular Weight |
416.64
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| Exact Mass |
416.33
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| Elemental Analysis |
C, 77.84; H, 10.65; O, 11.52
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| CAS # |
32222-06-3
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| Related CAS # |
(1S)-Calcitriol;61476-45-7;Calcitriol-d6;78782-99-7;Calcitriol-13C3;Calcitriol-d3;128723-16-0;Calcitriol Derivatives;2070009-24-2
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| PubChem CID |
5280453
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
565.0±50.0 °C at 760 mmHg
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| Melting Point |
119-121°C
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| Flash Point |
238.4±24.7 °C
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| Vapour Pressure |
0.0±3.5 mmHg at 25°C
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| Index of Refraction |
1.547
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| LogP |
6.12
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| tPSA |
60.69
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| 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
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| InChi Key |
GMRQFYUYWCNGIN-NKMMMXOESA-N
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| InChi Code |
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
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| Chemical 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
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. (3). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.75 mg/mL (6.60 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (6.60 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.75 mg/mL (6.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.75 mg/mL (6.60 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.75 mg/mL (6.60 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 6: ≥ 2.5 mg/mL (6.00 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 7: ≥ 2.5 mg/mL (6.00 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 8: ≥ 2.5 mg/mL (6.00 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 9: 0.55 mg/mL (1.32 mM) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4002 mL | 12.0008 mL | 24.0015 mL | |
| 5 mM | 0.4800 mL | 2.4002 mL | 4.8003 mL | |
| 10 mM | 0.2400 mL | 1.2001 mL | 2.4002 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05415254 | Recruiting | Drug: Calcitriol | COVID-19 Vitamin D Deficiency |
RenJi Hospital | June 12, 2022 | Not Applicable |
| NCT03748966 | Recruiting | Drug: Calcitriol | X-linked Hypophosphatemia Hypophosphatemic Rickets |
Massachusetts General Hospital | March 28, 2019 | Early Phase 1 |
| NCT05902078 | Not yet recruiting | Drug: Eldecalcitol capsules Drug: Calcitriol capsules |
Low Bone Mineral Density Postmenopausal Osteoporosis |
Shanghai Jiao Tong University Affiliated Sixth People's Hospital |
June 2023 | Phase 4 |
| NCT05298163 | Not yet recruiting | Drug: Calcitriol capsules Drug: Placebo |
Diabetic Kidney Disease | Indonesia University | April 2022 | Not Applicable |
| NCT02859896 | Active Recruiting |
Drug: Doxercalciferol (GZ427397) Drug: Calcitriol |
Secondary Hyperparathyroidism -Chronic Kidney Disease |
Sanofi | Phase 3 | Phase 3 |
 Calcipotriol inducedERαexpression in ER-negative breast cancer cells.
Calcitriol induced ERαprotein expression.BMC Cancer.2014 Mar 29;14:230. doi: 10.1186/1471-2407-14-230. |
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 Immunocytochemical analysis of ERαand VDR in primary and established breast cancer cells.BMC Cancer.2014 Mar 29;14:230. doi: 10.1186/1471-2407-14-230.
Calcitriol induced a fully active ERα.BMC Cancer.2014 Mar 29;14:230. doi: 10.1186/1471-2407-14-230. |
 Calcitriol inducedERαmRNA expression through the VDR in ERα-negative breast cancer cells.BMC Cancer.2014 Mar 29;14:230. doi: 10.1186/1471-2407-14-230. |
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