VDR

The proinflammatory cytokine KC is not affected by calcidiol or calcifediol in an ethanol solution when it comes to Pseudomonas-infected epithelial cells. Lethality of human bronchitis 16-HBE cells infected with calcifediol or calcifediol in ethanol solution was significantly reduced [1].

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Vitamin D reduced the viability of MCF-7 cells and promoted their apoptosis. Vitamin D enhanced VDR expression and induced DNA damage. When CD133+ stem cells were separated from MCF-7 cells, the IC50 of tamoxifen for stem cells was significantly higher than that of parental MCF-7 cells, suggesting a higher tamoxifen resistance in MCF-7 stem cells. Levels of VDR expression and Wnt/β-catenin signaling in CD133+ cells were markedly lower and higher than those in CD133- cells, respectively. Stem cells transfected with VDR overexpression plasmids showed decreased tamoxifen IC50 values, viability, spheroid formation, and expression of Wnt and β-catenin proteins when compared with control cells. Cell apoptosis was increased by transfection with a VDR overexpression plasmid. Finally, the inhibitory effects induced by VDR overexpression could be reversed by the VDR inhibitor, calcifediol. Conclusion: Stem cells contributed to the tamoxifen resistance of MCF-7 cells. Vitamin D-induced VDR expression increased the sensitivity of MCF-7 stem cells to tamoxifen by inhibiting Wnt/β-catenin signaling[2].

For three days, 50 ng/d of calcifediol or vehicle alone was injected into spontaneously hypertensive rats and normotensive Wistar-Kyoto (WKY) rats. In the control SHR, cellular Ca2+ flux and calbindin-D9K were found to be reduced. Calcifediol elevated brush border and total cell calbindin-D9K. On the other hand, for plasma calcitriol levels comparable to those in WKY rats, Ca2+ flux, which rose in vit-D animals, stayed lower in SHR.

MCF-7 cells were treated with 1,25(OH)2D3 and their levels of VDR expression, viability, and apoptosis were detected. CD133+ MCF-7 stem cells were identified and transfected with a VDR-overexpression plasmid. The tamoxifen concentration that reduced MCF-7 cell viability by 50% (IC50) was determined. The activation of Wnt/β-catenin signaling was also investigated[2].

50 ng/d; injection
Rats

Absorption, Distribution and Excretion
Readily absorbed.

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Metabolism / Metabolites
Calcidiol undergoes hydroxylation in the mitochondria of kidney tissue, and this reaction is activated by the renal 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to produce calcitriol (1,25- dihydroxycholecalciferol), the active form of vitamin D3.

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Biological Half-Life
288 hours

[1]. Calcifediol-loaded liposomes for local treatment of pulmonary bacterial infections. Eur J Pharm Biopharm. 2016 Nov 22.

[2]. Vitamin D-induced vitamin D receptor expression induces tamoxifen sensitivity in MCF-7 stem cells via suppression of Wnt/β-catenin signaling. Biosci Rep. 2018 Dec 7;38(6):BSR20180595.

Calcifediol monohydrate is a vitamin D.
The major circulating metabolite of vitamin D3 (cholecalciferol). It is produced in the liver and is the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties.
Calcifediol is an orally available synthetic form of the calcitriol prohormone calcifediol (25-hydroxyvitamin D), which can be used for vitamin D supplementation, and with potential immunomodulating activity. Upon oral administration, calcifediol is taken up by the body and converted, in the kidneys, to the active form calcitriol (1,25-dihydroxyvitamin D or 1,25(OH)2D). This form increases and normalizes vitamin D plasma levels, which, in turn, regulates calcium plasma levels, and normalizes elevated parathyroid hormone (PTH) levels by suppressing both PTH synthesis, and secretion. Vitamin D modulates and enhances the innate and adaptive immune responses. This may improve unregulated inflammation and prevents the production of pro-inflammatory cytokines. Specifically, vitamin D binds to its receptor vitamin D receptor (VDR) which is widely expressed on immune cells and epithelial cells. This stimulates neutrophils, macrophages, and natural killer (NK) cells, and activates epithelial cells to produce antimicrobial peptides (AMPs). In addition, upon infection, vitamin D promotes the migration of myeloid dendritic cells (mDCs) to lymphoid organs where they activate B- and T-lymphocytes.
The major circulating metabolite of VITAMIN D3. It is produced in the LIVER and is the best indicator of the body's vitamin D stores. It is effective in the treatment of RICKETS and OSTEOMALACIA, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties.

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Drug 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.
Treatment of secondary hyperparathyroidism (SHPT)

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Mechanism of Action
Calcidiol is transformed in the kidney by 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to calcitriol, the active form of vitamin D3. Calcitriol binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.

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Pharmacodynamics
Calcidiol is the precursor of vitamin D3. Vitamin D3 is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of vitamin A. The classical manifestations of vitamin D deficiency is rickets, which is seen in children and results in bony deformaties including bowed long bones. Deficiency in adults leads to the disease osteomalacia. Both rickets and osteomalacia reflect impaired mineralization of newly synthesized bone matrix, and usually result from a combination of inadequate exposure to sunlight and decreased dietary intake of vitamin D. Common causes of vitamin D deficiency include genetic defects in the vitamin D receptor, severe liver or kidney disease, and insufficient exposure to sunlight. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma.

C27H46O3

418.66

418.344

C, 77.46; H, 11.08; O, 11.46

63283-36-3

Calcifediol;19356-17-3;Calcifediol-d6 monohydrate;2483831-70-3;Calcifediol-13C5 monohydrate

6441383

White to off-white solid powder

529.2ºC at 760 mmHg

221.4ºC

2.07E-13mmHg at 25°C

6.733

3

3

6

30

655

5

C[C@H](CCCC(C)(C)O)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@H](CCC3=C)O)C.O

WRLFSJXJGJBFJQ-WPUCQFJDSA-N

InChI=1S/C27H44O2.H2O/c1-19-10-13-23(28)18-22(19)12-11-21-9-7-17-27(5)24(14-15-25(21)27)20(2)8-6-16-26(3,4)29/h11-12,20,23-25,28-29H,1,6-10,13-18H2,2-5H31H2/b21-11+,22-12-/t20-,23+,24-,25+,27-/m1./s1

(S,Z)-3-(2-((1R,3aS,7aR,E)-1-((R)-6-hydroxy-6-methylheptan-2-yl)-7a-methyloctahydro-4H-inden-4-ylidene)ethylidene)-4-methylenecyclohexan-1-ol hydrate

U 32070E; U-32070E; 63283-36-3; Calcifediol (monohydrate); Calderol; Calcifediol hydrate; Hidroferol; Didrogyl; U32070E; 2,5-Hydroxyvitamin D3 monohydrate; Calderol Dedrogyl Rayaldee

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~119.43 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.97 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 25.0 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.97 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.

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 (Please use freshly prepared in vivo formulations for optimal results.)