Calcitriol 是活性最大的维他命D代谢物，也是维他命D 受体激动剂。

Calcitriol is the physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.

Calcitriol is a potent inhibitor of PHA-induced lymphocyte proliferation, achieving 70% inhibition of tritiated thymidine incorporation after 72 h in culture. Calcitriol suppresses interleukin-2 (IL-2) production by PHA-stimulated peripheral blood mononuclear cells in a concentration-dependent fashion. [1] Calcitriol increases the concentration of intracellular calcium ([Ca2+]i) within 5 s by mobilizing calcium from the endoplasmic reticulum and the formation of inositol 1,4, 5-trisphosphate and diacylglycerol. [2] Calcitriol can inhibit the proliferation and promote the differentiation of human prostate adenocarcinoma cells. Calcitriol causes a selective decrease in the secreted levels of type IV collagenases (MMP-2 and MMP-9). [3] Calcitriol has antiproliferative activity in squamous cell carcinoma and prostatic adenocarcinoma and enhances the antitumor activity of platinum-based agents. Calcitriol prior to paclitaxel significantly reduces clonogenic survival compared with either agent alone in the murine squamous cell carcinoma and PC-3 cells. [4] Calcitriol is a potent anti-proliferative agent in a wide variety of malignant cell types. Calcitriol effects are associated with an increase in G0/G1 arrest, induction of apoptosis and differentiation, modulation of expression of growth factor receptors. Calcitriol potentiates the antitumor effects of many cytotoxic agents and inhibits motility and invasiveness of tumor cells and formation of new blood vessels. [5]

Combinations of Calcitriol with aromatase inhibitors or the analog EB1089 with all-trans-retinoic acid exhibit enhanced inhibition of the growth of MCF-7 xenografts. Calcitriol also exhibits potent anti-angiogenic activity that could contribute to its actions to inhibit invasion and metastasis[6]. Body-weight of HFD-fed animals become different as it gradually but noticeably decreased in Calcitriol group (150 IU/kg/day, p.o.) compared with controls after 12 weeks of treatment (11.4% versus 30.2%, p<0.05). At the end of the study, the animals that receive HFD with Calcitriol has the smallest percentage weight gain as opposed to control mice (6.8% versus 28.7%, p<0.01)[7].

Calcitriol is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1]. Experiments are performed using parathyroid tissue slices instead of dispersed parathyroid cells so that tissue architecture is maintained. Parathyroid glands are cut into small pieces of approximately 1 mm3 and placed in individual wells (24 well dishes) with constant shaking at 37°C and placed in an incubator with a humid atmosphere. The incubation medium is buffered (pH 7.4) and contained 125 mM NaCl, 5.9 mM KCl, 0.5 mM MgCl2, 1 mM NaH2PO4, and Na2HPO4 (1:2 ratio), 1 mM Na-pyruvate, 4 mM glutamine, 12 mM glucose, and 25 mM HEPES. Insulin 0.1 IU/mL, bovine serum albumin 0.1%, penicillin G 100 IU/mL, and streptomycin 100 μg/mL are added to the medium. CaCl2 is added to achieve a final target ionized calcium concentration of 1.25 mM as measured with a selective electrode (634 Ca/pH analyzer). Ionized calcium concentration is also measured in each well after the completion of the experiment, and no change in the ionized calcium concentration is observed. Calcitriol is added to the medium to achieve concentrations ranging from 10-10 to 10-7 M. To quantify the amount of free Calcitriol, we filtered the medium through a membrane with a 5000-MW cutoff and Calcitriol is measured by RIA (Gamma 1,25-Dihydroxyvitamin D). As compared with total Calcitriol, the concentration of free Calcitriol is decreased by one order of magnitude[1].

32222-06-3

C27H44O3

416.646

骨化三醇;1,25-Dihydroxyvitamin D3;Calcijex;RO215535;Topitriol;Rocaltrol

H2O:<1 mgml
Ethanol:77 mg/mL (184.8 mM)
DMSO:77 mg/mL (184.8 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years