VDR/vitamin D receptor; Human Endogenous Metabolite

骨化二醇诱导 CYP24A1 表达，EC50 为 70 nM。凝血酶表达由骨化二醇诱导，EC50 为 10-100 nM。根据共聚焦显微镜检查结果，用骨化三醇处理的细胞中的 VDR 定位模式相似，0.1-10 μM 骨化二醇以剂量依赖性方式诱导 VDR 易位到细胞核中。

三天内，将 50 ng/d 的骨化二醇或单独的载体注射到自发性高血压大鼠和正常血压 Wistar-Kyoto (WKY) 大鼠中。在对照 SHR 中，发现细胞 Ca2+ 通量和钙结合蛋白-D9K 减少。骨化二醇升高刷状缘和总细胞钙结合蛋白-D9K。另一方面，对于与 WKY 大鼠相当的血浆骨化三醇水平，在 vit-D 动物中升高的 Ca2+ 通量在 SHR 中保持较低。

用1,25（OH）2D3处理MCF-7细胞，检测其VDR表达、存活率和凋亡水平。鉴定CD133+MCF-7干细胞，并用VDR过表达质粒转染。测定了将MCF-7细胞存活率降低50%的他莫昔芬浓度（IC50）。还研究了Wnt/β-catenin信号传导的激活[2]。

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.
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.
Half Life: 288 hours

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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.

Calcidiol is a hydroxycalciol that is calciol in which the hydrogen at position 25 has been replaced by a hydroxy group. A prehormone resulting from the oxidation of calciol in the liver, it is further hydroxylated in the kidney to give calcitriol, the active form of vitamin D3. It has a role as a bone density conservation agent, a nutraceutical, a metabolite, a human metabolite and a mouse metabolite. It is a hydroxycalciol, a member of D3 vitamins and a diol.
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 anhydrous is a Vitamin D3 Analog.
Calcifediol has been reported in Solanum glaucophyllum and Homo sapiens with data available.
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.
Calcifediol Anhydrous is the anhydrous form of calcifediol, 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 (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.
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.

C27H44O2

400.64

400.334

C, 80.94; H, 11.07; O, 7.99

19356-17-3

Calcifediol monohydrate;63283-36-3;Calcifediol-d3;140710-94-7

5283731

White to off-white solid powder

1.0±0.1 g/cm3

529.2±33.0 °C at 760 mmHg

74-76oC

221.4±20.0 °C

0.0±3.2 mmHg at 25°C

1.536

7.53

40.46

2

2

6

29

655

5

O([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])[C@@]([H])(C([H])([H])[H])[C@@]1([H])C([H])([H])C([H])([H])[C@@]2([H])/C(=C(\[H])/C(/[H])=C3\C(=C([H])[H])C([H])([H])C([H])([H])[C@@]([H])(C\3([H])[H])O[H])/C([H])([H])C([H])([H])C([H])([H])[C@]12C([H])([H])[H]

JWUBBDSIWDLEOM-DTOXIADCSA-N

InChI=1S/C27H44O2/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,1,6-10,13-18H2,2-5H3/b21-11+,22-12-/t20-,23+,24-,25+,27-/m1/s1

(1S,3Z)-3-[(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-methylidenecyclohexan-1-ol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.24 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (5.19 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (5.19 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 2% DMSO +30% PEG 300 +5% Tween+ddH2O: 5mg/mL

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。