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Purity: ≥98%
Doxercalciferol (1α-hydroxyvitamin D2; 1alpha-hydroxy VD2), a synthetic vitamin D2 analog, is a potent agonist/activator of VDR (Vitamin D receptor) with important biological activities. It suppresses parathyroid synthesis and secretion, and has been used to treat secondary hyperparathyroidism and metabolic bone disease. Doxercalciferol (100 or 300 pg/g b.w.) normalizes serum calcium and parathyroid hormone (PTH) levels in nephrectomy treated mice. Doxercalciferol (300 pg/g b.w.) significantly reduces osteitis fibrosa in nephrectomy treated mice. Doxercalciferol results in significant decrease in cardiac hypertrophy and improves cardiac function in rats fed a high salt (HS) diet. Doxercalciferol treatment leads to a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level in rats fed a high salt (HS) diet.
| Targets |
Vitamin D receptor
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| ln Vitro |
In mice undergoing nephrectomy, doxercalciferol (100 or 300 pg/g b.w.) restores serum calcium and parathyroid hormone (PTH) levels to normal. In mice undergoing nephrectomy, doxercalciferol (300 pg/g b.w.) significantly lowers osteitis fibrosa. In rats given a high-salt (HS) diet, doxercalciferol significantly reduces cardiac hypertrophy and enhances cardiac function. In rats fed a high salt (HS) diet, doxercalciferol treatment results in a significant decrease in tissue atrial natriuretic factor (ANF) mRNA level and plasma brain natriuretic peptide (BNP) level. Additionally, doxercalciferol dramatically lowers protein kinase C-α (PKCα) levels, indicating a possible link between vitamin D deficiency and PKC-mediated cardiac hypertrophy. In diet-induced obese (DIO) mice, doxercalciferol reduces proteinuria, podocyte damage, mesangial growth, and extracellular matrix protein accumulation. In DIO mice, doxercalciferol also reduces profibrotic growth factors, proinflammatory cytokines, oxidative stress, and macrophage infiltration. Moreover, doxercalciferol inhibits the DIO mice's renin-angiotensin-aldosterone system activation, which includes the angiotensin II type 1 receptor and the mineralocorticoid receptor. In mice, the combination of doxercalciferol and losartan most effectively prevents albuminuria, restores the structure of the glomerular filtration barrier, and significantly lowers glomerulosclerosis in a dose-dependent manner. Mice's diabetic kidneys show virtually no morphological or molecular changes when doxercalciferol and losartan are combined.
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| ln Vivo |
In 5/6 nephrectomized (NX) rats, Doxercalciferol (0.083, 0.167, or 0.333 μg/kg, i.p.) raises serum phosphorus at Week 6. In addition, doxercalciferol (0.167 and 0.333 μg/kg) enhances increased pulse wave velocity (PWV) in 5/6 nephrectomized (NX) rats at Week 6 and raises serum calcium and Ca × P at Weeks 2 and 6. Doxercalciferol decreases serum PTH to the SHAM level and prevents PTH from rising at 0.083 μg/kg[1]. In NON mice fed a high-fat diet, doxercalciferol (125 ng/kg, i.p., three times a week) increases the expression of VDR mRNA level and renal expression of TRPV5. In mice given an HF diet, doxercalciferol also reduces proteinuria, stops podocyte loss, and reduces the buildup of extracellular matrix proteins. In mice fed an HF diet, doxercalciferol blocks increased expression of the renin-angiotensin-aldosterone system and inhibits the expression of profibrotic growth factors (TGF-β, PAI-1, and connective tissue growth factor (CTGF)). In addition, Doxercalciferol inhibits the infiltration of macrophages, lowers NF-κb activity, stops the expression of proinflammatory cytokines, and stops the accumulation of renal lipids in mice given a high-fat diet[2]. When administered intraperitoneally (i.p.) three times a week to streptozotocin-induced diabetic mice, doxercalciferol (30 ng/kg) significantly attenuates podocyte loss and apoptosis and decreases glomerular fibrosis[3].
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| Animal Protocol |
Rats: One week following nephrectomy, male Sprague-Dawley 5/6 nephrectomized (NX) rats (∼200 mg) are used. A typical surgical ablation procedure consisting of two steps is used to perform the nephrectomy. Rats are kept on a high-phosphorus diet (0.9% phosphorus and 0.6% calcium) for the duration of the study starting two weeks after nephrectomy in order to cause secondary hyperparathyroidism. Day 0: Vehicle (5% EtOH/95% propylene glycol; 0.4 mL/kg; i.p.) or VDRA (paricalcitol or Doxercalciferol; 0.083, 0.167, or 0.333 μg/kg; intraperitoneally) is given three times a week for 41 days (n = 6–10 per group) to SHAM and 5/6 NX rats (n = 7–10 per group). These dosages were selected because, in this CKD model, after two or six weeks of treatment, lower doses (0.021 and 0.042 μg/kg; i.p.) of either compound do not suppress PTH. Days 0 through 41 are when blood is drawn (24 hours after the dose). Animals are given ketamine (50 mg/kg) anesthesia on Days 0, 13, and 41 (24 h post-dose), and blood is drawn from the tail vein for measurements of PTH and serum blood chemistry[1].
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| References |
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| Molecular Formula |
C28H44O2
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| Molecular Weight |
412.65
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| Exact Mass |
412.33
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| Elemental Analysis |
C, 81.50; H, 10.75; O, 7.75
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| CAS # |
54573-75-0
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| Related CAS # |
trans-Doxercalciferol;74007-20-8;Impurity of Doxercalciferol;127516-23-8
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| Appearance |
White to yellow/brown solid powder
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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-CGMHZMFXSA-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,5Z)-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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| 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 |
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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: ≥ 2.5 mg/mL (6.06 mM) (saturation unknown) in 10% DMSO + 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 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: ≥ 2.5 mg/mL (6.06 mM) (saturation unknown) in 10% DMSO + 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 DMSO stock solution to 900 μL of corn oil and mix evenly. (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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02859896 | Active Recruiting |
Drug: Doxercalciferol (GZ427397) Drug: Calcitriol |
Secondary Hyperparathyroidism- Chronic Kidney Disease |
Sanofi | January 19, 2017 | Phase 3 |
| NCT00889629 | Completed | Drug: Doxercalciferol Drug: placebo |
Chronic Kidney Disease Kidney Transplantation |
Mariana Markell | November 2008 | Phase 4 |
| NCT00285467 | Completed | Drug: doxercalciferol Drug: Cholecalciferol |
Renal Osteodystrophy | Indiana University School of Medicine |
January 2006 | Not Applicable |
| NCT02282813 | Completed | Drug: Doxercalciferol Drug: Calcitriol |
Chronic Kidney Disease Vitamin D Deficiency |
OPKO Health, Inc. | April 2013 | Phase 3 |
| NCT00792857 | Completed | Drug: CTAP201 Injection Drug: Doxercalciferol |
Chronic Kidney Disease Chronic Renal Failure |
OPKO IP Holdings II, Inc. | November 2008 | Phase 1 |
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