Calcifediol|19356-17-3|安捷凯

Background

Vitamin D receptor (VDR) activation is associated with cardiovascular and survival benefits in chronic kidney disease patients. Calcifediol, also known as calcidiol, is a prehormone that is produced in the liver by hydroxylation of vitamin D3.

In vitro: Calcifediol induced CYP24A1 expression with EC50 at 70 nM. Calcifediol stimulated the expression of thrombomodulin with EC50 at 10-100 nM. Confocal microscopy revealed that calcifediol at 0.1 - 10 μM induced VDR translocation into the nucleus dose-dependently; the VDR localization pattern was similar in cells treated with calcitriol [1].

In vivo: Spontaneously hypertensive rats and normotensive Wistar-Kyoto (WKY) rats were injected with either 50 ng/d calcifediol or vehicle alone for 3 days. Decreased calbindin-D9K and cellular Ca2+ flux were observed in control SHR. Calcifediol increased total cell and brush border calbindin-D9K. In contrast, Ca2+ flux, which increased in vit-D animals, remained lower in SHR for plasma calcitriol levels similar to those in WKY rats [2].

Clinical trial: Calcifediol given daily, weekly, or as a single bolus is about 2-3 times more potent in increasing plasma 25(OH)D3 concentrations than vitamin D3. Plasma 25(OH)D3 concentrations of 30 ng/mL were reached more rapidly and reliably with calcifediol [3].

Reference:
[1] Wu-Wong JR, Chen YW, Nakane M, Wolf M.? Differential effects of vitamin d receptor agonists on gene expression in neonatal rat cardiomyocytes. Cardiovasc Drugs Ther. 2011 Jun;25(3):215-22.
[2] Roullet CM, Roullet JB, Martin AS, McCarron DA.? In vivo effect of calcitriol on calcium transport and calcium binding proteins in the spontaneously hypertensive rat. Hypertension. 1994 Aug;24(2):176-82.
[3] Jetter A, Egli A, Dawson-Hughes B, Staehelin HB, Stoecklin E, Goessl R, Henschkowski J, Bischoff-Ferrari HA.? Pharmacokinetics of oral vitamin D(3) and calcifediol. Bone. 2014 Feb;59:14-9.

Protocol

Cell experiment [1,2]:

Cell lines

Neonatal rat cardiomyocytes, plasmacyoid dendritic cells (pDCs) and conventional DCs

Preparation method

The solubility of this compound in DMSO is >13.65mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0.1-10 μM, 2 hours

Applications

Calcifediol induced CYP24A1 expression with EC50 of 70 nM. Calcifediol stimulated the expression of thrombomodulin with EC50 at 10-100 nM. Calcifediol (0.1-10 μM) dose-dependently induced VDR translocation into the nucleus. Calcifediol led to significant expression of Cyp24A1 in moDCs after 16 hours.

Animal experiment [2]:

Animal models

Wistar-Kyoto rats

Dosage form

50 ng/d calcifediol for 3 days

Application

In spontaneously hypertensive rats and normotensive Wistar-Kyoto (WKY) rats, calcifediol (50 ng/d for 3 days), calcifediol increased total cell and brush border calbindin-D9K.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

参考文献:

[1]. Wu-Wong J R, Chen Y W, Nakane M, et al. Differential effects of vitamin d receptor agonists on gene expression in neonatal rat cardiomyocytes[J]. Cardiovascular drugs and therapy, 2011, 25(3): 215-222.

[2]. Karthaus N, Van Spriel A B, Looman M W G, et al. Vitamin D controls murine and human plasmacytoid dendritic cell function[J]. Journal of Investigative Dermatology, 2014, 134(5): 1255-1264.

[3]. Roullet C M, Roullet J B, Martin A S, et al. In vivo effect of calcitriol on calcium transport and calcium binding proteins in the spontaneously hypertensive rat[J]. Hypertension, 1994, 24(2): 176-182.

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Calcifediol

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