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| Targets |
trans-Doxercalciferol targets the vitamin D receptor (VDR), a nuclear receptor that regulates gene expression involved in calcium and phosphate homeostasis, bone metabolism, and immune function. As the trans-isomer of Doxercalciferol, it functions as a VDR agonist. Doxercalciferol is a vitamin D₂ analog that, upon hepatic activation to 1α-hydroxyvitamin D₂, binds to VDR with high affinity. VDR activation leads to the transcriptional regulation of target genes, including those involved in calcium absorption in the intestine, calcium reabsorption in the kidney, and bone remodeling. The compound's reduced risk of hypercalcemia compared to other vitamin D analogs makes it a potentially safer option for therapeutic applications.
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| ln Vitro |
In vitro, trans-Doxercalciferol serves primarily as an analytical reference standard rather than an active pharmacological agent in cell-based assays. The parent compound Doxercalciferol demonstrates VDR agonist activity in vitro, promoting the differentiation of various cell types, including osteoblasts and immune cells. VDR activation by Doxercalciferol leads to the upregulation of CYP24A1 (24-hydroxylase), which is involved in vitamin D metabolism, and the downregulation of PTH (parathyroid hormone) expression. The compound also exhibits antiproliferative and pro-differentiation effects in various cancer cell lines. trans-Doxercalciferol's in vitro activity is primarily relevant to analytical method development for quality control applications.
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| ln Vivo |
In vivo, Doxercalciferol is used as a therapeutic agent for the prevention and treatment of secondary hyperparathyroidism in patients with chronic kidney disease. It is administered orally and undergoes hepatic activation to form 1α-hydroxyvitamin D₂, the active metabolite that regulates calcium and phosphorus homeostasis. Doxercalciferol effectively suppresses parathyroid hormone (PTH) levels while maintaining calcium and phosphorus within acceptable ranges, with a reduced risk of hypercalcemia compared to other vitamin D analogs. trans-Doxercalciferol, as the trans-isomer, is not used therapeutically but serves as an analytical standard for monitoring the quality and purity of Doxercalciferol pharmaceutical products.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cellular) assays for trans-Doxercalciferol are not standard pharmacological assays, as the compound is primarily an analytical reference standard. However, binding studies may be performed to investigate its interaction with the vitamin D receptor (VDR) using techniques such as surface plasmon resonance (SPR) or radioligand binding assays. In these assays, VDR protein is immobilized on a sensor chip or incubated with radiolabeled vitamin D and varying concentrations of the test compound. The binding affinity (Kd) is calculated from binding curves. Additionally, VDR-mediated transcriptional activity can be assessed using cell-free reporter gene systems. These assays help characterize the compound's receptor binding properties and compare them to the parent compound Doxercalciferol.
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| Cell Assay |
In vitro cellular experiments with trans-Doxercalciferol are not typically performed for pharmacological evaluation, as the compound serves as an analytical reference standard rather than a therapeutic agent. However, cellular assays for VDR agonists may be conducted using cell lines such as MG-63 (osteosarcoma), HL-60 (promyelocytic leukemia), or Caco-2 (colorectal adenocarcinoma). Cells are cultured in appropriate media and treated with varying concentrations of the compound for 24-72 hours. VDR activation is assessed by measuring the expression of VDR target genes (e.g., CYP24A1, osteocalcin) using RT-qPCR or by detecting changes in cell proliferation or differentiation. The compound's activity is compared to that of the parent compound Doxercalciferol.
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| Animal Protocol |
In vivo animal studies with trans-Doxercalciferol are not typically performed for therapeutic development, as the compound is an analytical reference standard. For the parent compound Doxercalciferol, in vivo efficacy studies are performed in animal models of chronic kidney disease and secondary hyperparathyroidism. Rodents with induced renal failure are administered Doxercalciferol via oral gavage at various doses. Efficacy is assessed by measuring serum PTH, calcium, and phosphorus levels. Bone histomorphometry may be performed to evaluate the effects on bone remodeling. The compound's reduced risk of hypercalcemia compared to other vitamin D analogs is an important safety endpoint in these studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of trans-Doxercalciferol are derived from the parent compound Doxercalciferol. Doxercalciferol has a molecular weight of 412.65 and molecular formula C₂₈H₄₄O₂. It is administered orally and undergoes hepatic activation to form 1α-hydroxyvitamin D₂. Doxercalciferol has a long half-life and is extensively bound to vitamin D-binding protein in plasma. It is metabolized primarily in the liver by CYP24A1 and other cytochrome P450 enzymes to various metabolites, which are excreted in bile and urine. The compound's reduced risk of hypercalcemia compared to other vitamin D analogs is attributed to its pharmacokinetic and pharmacodynamic properties. Storage: 2-8°C in an amber vial, under inert atmosphere.
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| Toxicity/Toxicokinetics |
Toxicological information for trans-Doxercalciferol is derived from the parent compound Doxercalciferol. Doxercalciferol is generally well-tolerated, with the most common adverse effects being hypercalcemia, hyperphosphatemia, and gastrointestinal disturbances. The compound's reduced risk of hypercalcemia compared to other vitamin D analogs is a key safety advantage. As a vitamin D analog, Doxercalciferol should be used with caution in patients with hypercalcemia, vitamin D toxicity, or calcium-containing kidney stones. trans-Doxercalciferol, as a research compound, should be handled with appropriate safety precautions, including use of personal protective equipment (gloves, safety goggles, lab coat) and working in a well-ventilated area. The compound is for research use only and is not approved for clinical use.
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| References | |
| Additional Infomation |
See also: Docecalciferol (note moved to).
trans-Doxercalciferol (CAS 74007-20-8) is the trans-isomer of Doxercalciferol, a synthetic vitamin D₂ analog that functions as a vitamin D receptor (VDR) agonist. The compound has molecular formula C₂₈H₄₄O₂ and molecular weight 412.65. It appears as an off-white solid. Doxercalciferol is a prohormone that undergoes hepatic activation to form 1α-hydroxyvitamin D₂, an active metabolite that regulates calcium and phosphorus homeostasis. trans-Doxercalciferol is used as an analytical standard for method development, validation, and quality control applications during the production of Doxercalciferol. The compound is characterized by a reduced risk of hypercalcemia compared to other vitamin D analogs. Storage: 2-8°C in an amber vial, under inert atmosphere. |
| Molecular Formula |
C28H44O2
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|---|---|
| Molecular Weight |
412.6478
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| Exact Mass |
412.334
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| CAS # |
74007-20-8
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| Related CAS # |
Doxercalciferol;54573-75-0;Impurity of Doxercalciferol;127516-23-8
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| PubChem CID |
46705423
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| Appearance |
White to off-white solid powder
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| LogP |
6.611
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
712
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C[C@H](/C=C/[C@H](C)C(C)C)[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 |
HKXBNHCUPKIYDM-HBZIUUSASA-N
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| InChi Code |
InChI=1S/C28H44O2/c1-18(2)19(3)9-10-20(4)25-13-14-26-22(8-7-15-28(25,26)6)11-12-23-16-24(29)17-27(30)21(23)5/h9-12,18-20,24-27,29-30H,5,7-8,13-17H2,1-4,6H3/b10-9+,22-11+,23-12+/t19-,20+,24+,25+,26-,27-,28+/m0/s1
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| Chemical Name |
(1R,3S,5E)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-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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| 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 |
| 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) |
DMSO : ~50 mg/mL (~121.17 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4234 mL | 12.1168 mL | 24.2336 mL | |
| 5 mM | 0.4847 mL | 2.4234 mL | 4.8467 mL | |
| 10 mM | 0.2423 mL | 1.2117 mL | 2.4234 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.
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