Calcitriol
(Synonyms: 骨化三醇; 1,25-Dihydroxyvitamin D3) 目录号 : GC13852
骨化三醇作为类固醇激素维生素 D 的最具生物活性的代谢产物，抑制骨化三醇会导致抗癌药物的作用降低。
Cas No.:32222-06-3
Sample solution is provided at 25 µL, 10mM.
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Related Biological Data
VD reduces ferroptosis induced by high glucose in HK-2 cells and down-regulation of Klotho attenuates the protective effect of VD on ferroptosis in HK-2 cells. (F-K) Protein levels of SLC7A11, GPX4, TFR1, Klotho and p53 were detected by western blot.
HG + VD group (30 mmol/L D-glucose + 10 nmol/L 1,25(OH)2D3);1,25(OH)2D3 (GLPBIO, Beijing, China) was pretreated for 2 h before intervention.
Apoptosis (2024): 1-13. PMID: 38558206 IF: 7.2002 -
Related Biological Data
Effect of vitamin D deficiency on migration of human trophoblast cells. D&E: Cell migration was measured using wound-healing assay. After 12 and 24 h migration, the scratches were photographed and wounded areas were calculated.
And calcitriol (GLPBIO, China) was dissolved in DMSO at the final concentration of 1 mM, and the final concentration of calcitriol were 0.1 μM.
Placenta (2022). PMID: 36103800 IF: 3.2867
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
HL-1 cells |
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Preparation Method |
Calcitriol (1 and 10 nM) was used to treat HL-1 cells for 48 h to determine the initial dose-response effect. To study the functional relevance of FGFR1 modulation, recombinant mouse FGF-2 (25 ng/mL) was administrated (for 0.5 or 48 h) in control and calcitriol-treated HL-1 cells. |
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Reaction Conditions |
1 and 10 nM; 48 h |
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Applications |
Compared to control cells, as shown in Fig. 1a, calcitriol (1 and 10 nM) dose-dependently reduced FGFR1 protein expression in HL-1 cells by 31 and 62%, respectively. Similarly, calcitriol (10 nM)-treated HL-1 cells had lower FGFR1 mRNA expression than did control HL-1 cells. |
| Animal experiment [2]: | |
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Animal models |
Male C57BL/6J mice aged 4–5 weeks and weighing ~21–27 g |
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Preparation Method |
Four groups of mice (n = 11 each) were maintained on either low-fat diet (LFD) or high-fat diet (HFD) with and without 150 IU/kg/day calcitriol orally for 16 weeks. |
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Dosage form |
150 IU/kg/day; orally |
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Applications |
A significant gradual decrease in weight was observed in HFD-fed mice treated with calcitriol compared with a steady increase in controls. Furthermore, calcitriol treatment reduced concentrations of various inflammatory markers including TNF-α, CRP and IL-6. |
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References: [1]. Lee TW, et al. Calcitriol downregulates fibroblast growth factor receptor 1 through histone deacetylase activation in HL-1 atrial myocytes. J Biomed Sci. 2018 May 18;25(1):42. [2]. Alkharfy KM, et al. Calcitriol attenuates weight-related systemic inflammation and ultrastructural changes in the liver in a rodent model. Basic Clin Pharmacol Toxicol. 2013 Jan;112(1):42-9. |
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Calcitriol, as the most biologically active metabolite derived from the secosteroid hormone vitamin D, the inhibition of calcitriol caused decreased effects of anticancer drugs.[1]
In vitro efficacy test it shown that weekly oral administration of calcitriol allowed reach the peak serum calcitriol concentrations well above 1 nM, a concentration that inhibition more than 50% of prostate cancer proliferation. [2] With 10 nM calcitriol remarkably decreased RAGE protein expression and increased sRAGE concentrations in HL-1 cardiomyocytes compared with control cells.[3] Calcitriol exhibited antiproliferative effects against T47D, MCF-7, and MDA-MB-231 with IC50 values in the range of 0.05-0.25 μM.[4] In addition, calcitriol inhibits melanoma cell proliferation with an IC?? of 0.24 μM.[5] BT-474 cells were dose-dependently growth-inhibited by calcitriol with IC50 of 2.9 nM. With 1 nM Calcitriol synergistically improved AZD4547 antiproliferative effects, allowing a 2-fold AZD4547 dose-reduction. [6]
In vivo test it demonstrated that calcitriol (0.03 μg/kg) 5 times/wk intraperitoneally for 10 wk in UNX ApoE-/- mice caused significant vascular calcification and elevated expression of related proteins (BMP2, RANKL, and Runx2).[8] With 0.5 ug/day calcitriol orally improved insulin resistance and HOMA-β after 6 months in ND patients, however, only improved HOMA-β in the dialysis patients, with no obvious effect on insulin resistance.[7]
References:
[1]Ma J, et al. The mechanism of calcitriol in cancer prevention and treatment. Curr Med Chem. 2013;20(33):4121-30.?
[2]Beer TM. Development of weekly high-dose calcitriol based therapy for prostate cancer. Urol Oncol. 2003 Sep-Oct;21(5):399-405.?
[3]Lee TW, et al. ADAM10 modulates calcitriol-regulated RAGE in cardiomyocytes. Eur J Clin Invest. 2017 Sep;47(9):675-683.
[4]Aljunidee KA, et al. Combination therapy of calcitriol inhibits the proliferation of breast cancer cells: new concept of nonclassical function of calcitriol. Horm Mol Biol Clin Investig. 2021 Nov 15.?
[5]Sutedja EK, et al. Calcitriol Inhibits Proliferation and Potentially Induces Apoptosis in B16-F10 Cells. Med Sci Monit Basic Res. 2022 May 5;28:e935139.
? [6]Morales-Guadarrama G, et al. AZD4547 and calcitriol synergistically inhibited BT-474 cell proliferation while modified stemness and tumorsphere formation. J Steroid Biochem Mol Biol. 2022 May 31;223:106132.
[7]Lu Y, et al. Effects of active vitamin D on insulin resistance and islet β-cell function in non-diabetic chronic kidney disease patients: a randomized controlled study. Int Urol Nephrol. 2022 Jul;54(7):1725-1732.
[8]Becker LE, et al. Effect of paricalcitol and calcitriol on aortic wall remodeling in uninephrectomized ApoE knockout mice. Am J Physiol Renal Physiol. 2011 Mar;300(3):F772-82.
骨化三醇作为类固醇激素维生素 D 的最具生物活性的代谢产物,抑制骨化三醇会导致抗癌药物的作用降低。[1]
体外功效测试表明,每周口服骨化三醇可使血清骨化三醇浓度达到峰值,远高于 1 nM,该浓度可抑制超过 50% 的前列腺癌增殖。 [2] 与对照细胞相比,10 nM 骨化三醇可显着降低 HL-1 心肌细胞中 RAGE 蛋白的表达并增加 sRAGE 浓度。[3] 骨化三醇对 T47D、 MCF-7 和 MDA-MB-231 的 IC50 值在 0.05-0.25 μM 范围内。 [4]此外,骨化三醇抑制黑色素瘤细胞增殖,IC50 为 0.24 μM。[5] BT-474 细胞的生长受到剂量依赖性抑制,IC50 为 2.9 nM。与 1 nM 骨化三醇协同改善 AZD4547 的抗增殖作用,使 AZD4547 剂量减少 2 倍。 [6]
体内试验表明,在 UNX ApoE-/- 小鼠中,骨化三醇 (0.03 μg/kg) 腹腔注射 5 次/周,持续 10 周,导致显着的血管钙化和相关蛋白（BMP2、RANKL 和 Runx2）的表达升高。 [8] ND患者口服0.5 ug/天骨化三醇6个月后可改善胰岛素抵抗和HOMA-β,但仅改善透析患者的HOMA-β,对胰岛素抵抗无明显影响.[7]
| Cas No. | 32222-06-3 | SDF | |
| 别名 | 骨化三醇; 1,25-Dihydroxyvitamin D3 | ||
| 化学名 | (1R,3S,5Z)-5-[(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-methylidenecyclohexane-1,3-diol | ||
| Canonical SMILES | CC(CCCC(C)(C)O)C1CCC2C1(CCCC2=CC=C3CC(CC(C3=C)O)O)C | ||
| 分子式 | C27H44O3 | 分子量 | 416.64 |
| 溶解度 | ≥ 20.832mg/mL in DMSO | 储存条件 | -20°C, protect from light, stored under nitrogen,unstable in solution, ready to use. |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4002 mL | 12.0008 mL | 24.0015 mL |
| 5 mM | 0.48 mL | 2.4002 mL | 4.8003 mL |
| 10 mM | 0.24 mL | 1.2001 mL | 2.4002 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
TGF-beta and calcitriol
Gen Pharmacol1998 Feb;30(2):145-51.PMID: 9502167DOI: 10.1016/s0306-3623(97)00271-1
Vitamin D3 and transforming growth factor-beta (TGF-beta) are molecules from unrelated families that share identical actions on cell growth and differentiation. The active metabolite of vitamin D3, calcitriol (1alpha,25-dihydroxyvitamin D3), induces an inhibitory effect on the growth of various cell types, and the expression of different markers of cell differentiation. As the receptor of vitamin D3 is ubiquitous, these effects are widespread in the organism. TGF-beta is a growth factor produced by many cell types, and is a known inhibitor of the proliferation of epithelial cells. Because of the similarity in their actions, many studies have been aimed at defining some interactions between the two substances. The purpose of this article is to illustrate the nature of the interactions, and two examples are developed. In normal or transformed epithelial cells, it has been demonstrated that the inhibitory effect of calcitriol on cell growth could be related to an induction of TGF-beta synthesis, and of a paracrine/autocrine loop. In bone, where both compounds play a very important role on the mechanisms controlling bone formation and remodeling, the interplay is more complex, and even includes the receptors of the two substances. Interest in this topic is growing and will surely lead to the establishment of new links between those two compounds.
The mechanism of calcitriol in cancer prevention and treatment
Curr Med Chem2013;20(33):4121-30.PMID: 23895685DOI: 10.2174/09298673113209990195
Calcitriol (1, 25-dihydroxyvitamin D3) is the most biologically active metabolite derived from the secosteroid hormone vitamin D. Apart from its calcium homeostatic effects, epidemiological studies have shown that reduced serum calcitriol levels are associated with an increased risk of some types of cancer. Numerous recent epidemiological and experimental studies have reported that it elicits anti-proliferative, apoptotic and differentiation effects in several malignant cell types. The inhibition of calcitriol results in reduced effects of anticancer drugs. Results from a number of clinical trials revealed that sufficient dosing and exposure to calcitriol is critical for achieving antitumor effects during intermittent regimens. This review summarizes the role of calcitriol in anticancer therapy and the progress in understanding its mechanism.
Rapid Nontranscriptional Effects of Calcifediol and Calcitriol
Nutrients2022 Mar 18;14(6):1291.PMID: 35334948DOI: 10.3390/nu14061291
Classically, a secosteroid hormone, vitamin D, has been implicated in calcium and phosphate homeostasis and has been associated with the pathogenesis of rickets and osteomalacia in patients with severe nutritional vitamin D deficiency. The spectrum of known vitamin D-mediated effects has been expanded in recent years. However, the mechanisms of how exactly this hormone elicits its biological function are still not fully understood. The interaction of this metabolite with the vitamin D receptor (VDR) and, subsequently, with the vitamin D-responsive element in the region of specific target genes leading to the transcription of genes whose protein products are involved in the traditional function of calcitriol (known as genomic actions). Moreover, in addition to these transcription-dependent mechanisms, it has been recognized that the biologically active form of vitamin D3, as well as its immediate precursor metabolite, calcifediol, initiate rapid, non-genomic actions through the membrane receptors that are bound as described for other steroid hormones. So far, among the best candidates responsible for mediating rapid membrane response to vitamin D metabolites are membrane-associated VDR (VDRm) and protein disulfide isomerase family A member 3 (Pdia3). The purpose of this paper is to provide an overview of the rapid, non-genomic effects of calcifediol and calcitriol, whose elucidation could improve the understanding of the vitamin D3 endocrine system. This will contribute to a better recognition of the physiological acute functions of vitamin D3, and it could lead to the identification of novel therapeutic targets able to modulate these actions.
Synthetic studies of (23S,25R)-1α,25-dihydroxyvitamin D 3 26,23-lactone (calcitriol lactone) and its derivatives
J Steroid Biochem Mol Biol2018 Mar;177:240-246.PMID: 28757443DOI: 10.1016/j.jsbmb.2017.07.017
(23S,25R)-1α,25-Dihydroxyvitamin D3 26,23-lactone (calcitriol lactone) is a major metabolite of 1α,25-dihydroxyvitamin D3 that binds to vitamin D receptor (VDR) and exhibits various biological activities. This lactone and its derivatives are considered to have potential as drug candidates to treat VDR-related diseases, but their biological activities have not yet been fully characterized, mainly because of their limited availability by chemical synthesis. This review deals with synthetic studies of calcitriol lactone, and its derivatives, i.e., methylene lactones (TEI-9647 and its derivatives) and calcitriol lactams (DLAMs). We also discuss their biological activities, VDR-binding affinity and structure-activity relationships.
Calcitriol (Vectical) for mild to moderate plaque psoriasis
Med Lett Drugs Ther2009 Sep 7;51(1320):70-1.PMID: 19738550DOI: 10.1016/s1078-1439(03)00170-4
The FDA has approved calcitriol ointment (Vectical--Galderma), a vitamin D analog, for topical treatment of mild-to-moderate plaque psoriasis in adults >or = 18 years old. Ointments are generally considered more potent than creams or solutions.