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].

---

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
Easily absorbed. Metabolism/Metabolites Calcidiol undergoes hydroxylation in the mitochondria of kidney tissue. This reaction is activated by renal 25-hydroxyvitamin D3-1-(α)-hydroxylase to produce active vitamin D3—calcitriol (1,25-dihydroxycholecalciferol). 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.

Calcidiol monohydrate is a form of vitamin D. It is the major circulating metabolite of vitamin D3 (cholecalciferol). Synthesized in the liver, it is the best indicator of the body's vitamin D reserves. It is effective in treating rickets and osteomalacia, regardless of whether the patient has azotemia. Calcidiol also has mineralizing properties. Calcidiol is the oral synthetic form of the pro-hormone calcitriol (25-hydroxyvitamin D), used for vitamin D supplementation, and has potential immunomodulatory activity. After oral administration, calcidiol is absorbed by the body and converted in the kidneys to the active form, calcitriol (1,25-dihydroxyvitamin D or 1,25(OH)₂D). This form of vitamin D can increase and regulate plasma vitamin D levels, thereby regulating plasma calcium levels, and modulating elevated PTH levels by inhibiting the synthesis and secretion of parathyroid hormone (PTH). Vitamin D can regulate and enhance both innate and adaptive immune responses. This may improve uncontrolled inflammation and prevent the production of pro-inflammatory cytokines. Specifically, vitamin D binds to its receptor—the 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). Furthermore, during infection, vitamin D promotes the migration of myeloid dendritic cells (mDCs) to lymphoid organs, where they activate B cells and T cells. The main circulating metabolite of vitamin D3 is vitamin D produced by the liver, which is the best indicator of the body's vitamin D reserves. It is effective in treating rickets and osteomalacia, regardless of whether the patient has azotemia. Calcidiol also has mineralizing properties.

---

Pharmacological Indications
For the treatment of vitamin D deficiency or insufficiency, refractory rickets (vitamin D-resistant rickets), familial hypophosphatemia, and hypoparathyroidism, as well as hypocalcemia and renal osteodystrophy in patients with chronic renal failure undergoing dialysis.
It can also be used in combination with calcium supplements for the treatment and prevention of primary or corticosteroid-induced osteoporosis.
Treatment of secondary hyperparathyroidism (SHPT)
Mechanism of Action

Calcadiol is converted to active vitamin D3—calcitriol—in the kidneys by 25-hydroxyvitamin D3-1-(α)-hydroxylase. Calcitriol binds to intracellular receptors, which subsequently regulate gene expression as transcription factors. Like receptors for other steroid hormones and thyroid hormones, vitamin D receptors have both hormone-binding and DNA-binding domains. Vitamin D receptors form a complex with another intracellular receptor—the retinoid X receptor—which binds to DNA. In most studies, its role is to activate transcription, but there are also cases where vitamin D inhibits transcription. Calcitriol increases serum calcium concentration through: increased gastrointestinal absorption of phosphorus and calcium, increased osteoclast reabsorption of calcium, and increased distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal calcium absorption by binding to vitamin D receptors in the cytoplasm of intestinal mucosal cells. Calcium is then absorbed through the formation of calcium-binding proteins. Pharmacodynamics Calcitriol is a precursor to vitamin D3. Vitamin D3 is a steroid hormone whose important role in regulating calcium and phosphorus levels, bone mineralization, and vitamin A absorption is well-known. A typical manifestation of vitamin D deficiency is rickets, common in children, which leads to skeletal deformities, including curvature of long bones. In adults, vitamin D deficiency leads to osteomalacia. Both rickets and osteomalacia reflect impaired mineralization of newly synthesized bone matrix, usually resulting from a combination of insufficient sunlight exposure and reduced dietary vitamin D intake. Common causes of vitamin D deficiency include vitamin D receptor gene defects, severe liver or kidney disease, and insufficient sunlight exposure. Vitamin D plays an important role in maintaining calcium homeostasis and regulating parathyroid hormone (PTH). It promotes the reabsorption of calcium by the kidneys, increases the absorption of calcium and phosphorus in the intestines, and promotes the mobilization of calcium and phosphorus from bones 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.

---

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.

---

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