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度骨化醇

度骨化醇用途

Doxercalciferol 是维生素 D2 类似物，为维生素 D (Vitamin D) 受体激活剂，能够抵抗肾病的进程。

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度骨化醇名称

[ CAS 号 ]:
54573-75-0

[ 中文名 ]:
度骨化醇

[ 英文名 ]:
Doxercalciferol

[中文别名 ]:

1-Α羟基维生素D2

[英文别名 ]:

UNII-3DIZ9LF5Y9
doxercalciferol
MFCD01076571
Hectorol

度骨化醇生物活性

[ 描述 ]:

Doxercalciferol 是维生素 D2 类似物,为维生素 D (Vitamin D) 受体激活剂,能够抵抗肾病的进程。

[ 相关类别 ]:

信号通路 >> 维生素 D 相关 >> VD/VDR

研究领域 >> 代谢疾病

[ 靶点 ]

Vitamin D receptor[1]

[体内研究]

在5/6肾切除(NX)大鼠中,Doxercalciferol(0.083,0.167或0.333μg/ kg,ip)在第6周升高血清磷。 Doxercalciferol(0.167和0.333μg/ kg)也在第2周和第6周增加血清钙和Ca×P,并且在5/6肾切除(NX)大鼠中在第6周增强脉搏波速度(PWV)。 Doxercalciferol阻止PTH从0.083μg/ kg上升,并将血清PTH降低至SHAM水平[1]。在喂食HF饮食的NON小鼠中,Doxercalciferol(125ng/kg,每周三次ip)增加VDR mRNA水平的表达和TRPV5的肾脏表达。 Doxercalciferol还可改善HF饮食诱导的小鼠的蛋白尿,防止足细胞的丢失和细胞外基质蛋白的积累。 Doxercalciferol抑制促纤维化生长因子(TGF-β,PAI-1和结缔组织生长因子(CTGF))的表达,并阻断喂食HF饮食的小鼠肾素-血管紧张素-醛固酮系统的表达增加。此外,Doxercalciferol抑制巨噬细胞浸润,降低NF-κB活性,并预防喂食HF饮食的小鼠中促炎细胞因子的表达和肾脏脂质积累的增加[2]。 Doxercalciferol(30 ng/kg,每周三次ip)可预防白蛋白尿,显着减弱足细胞丢失和凋亡,并减少链脲佐菌素诱导的糖尿病小鼠肾小球纤维化[3]。

[动物实验]

大鼠[1]在肾切除术后1周使用雄性，Sprague-Dawley，5/6肾切除（NX）大鼠（~200gm）。使用标准的两步外科消融手术进行肾切除术。在肾切除术后2周开始，在研究期间将大鼠维持在高磷饮食（0.9％磷和0.6％钙）上以诱导继发性甲状旁腺功能亢进。在第0天，SHAM和5/6 NX大鼠（每组n = 7-10）接受载体（5％EtOH / 95％丙二醇; 0.4mL / kg; ip）或VDRA（帕立骨化醇或Doxercalciferol; 0.083,0.167或0.333μg/ kg;腹膜内）每周三次，持续41天（每组n = 6-10）。基于以下事实选择这些剂量：在该CKD模型中，在治疗2或6周后，任一化合物的较低剂量（0.021和0.042μg/ kg; ip）不是PTH抑制剂。在第0,13和41天，收集血液（给药后24小时）。在第0,13和41天（给药后24小时），用氯胺酮（50mg / kg）麻醉动物，并通过尾静脉收集血液用于PTH和血清血液化学测定[1]。

[参考文献]

[1]. Noonan W, et al. Differential effects of vitamin D receptor activators on aortic calcification and pulse wave velocity in uraemic rats. Nephrol Dial Transplant. 2008 Dec;23(12):3824-30.

[2]. Wang XX, et al. Vitamin D receptor agonist doxercalciferol modulates dietary fat-induced renal disease and renal lipid metabolism. Am J Physiol Renal Physiol. 2011 Mar;300(3):F801-10.

[3]. Wang Y, et al. Vitamin D receptor signaling in podocytes protects against diabetic nephropathy. J Am Soc Nephrol. 2012 Dec;23(12):1977-86.

[相关活性小分子]

度骨化醇物理化学性质

[ 密度 ]:
1.0±0.1 g/cm3

[ 沸点 ]:
538.7±50.0 °C at 760 mmHg

[ 熔点 ]:
138-140ºC

[ 分子式 ]:
C₂₈H₄₄O₂

[ 分子量 ]:
412.648

[ 闪点 ]:
224.0±24.7 °C

[ 精确质量 ]:
412.334137

[ PSA ]:
40.46000

[ LogP ]:
8.15

[ 外观性状 ]:
白色结晶粉末

[ 蒸汽压 ]:
0.0±3.3 mmHg at 25°C

[ 折射率 ]:
1.541

[ 储存条件 ]:
Desiccate at -20°C

度骨化醇MSDS

详细MSDS(安全技术说明书)

度骨化醇毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: VS2950000

CHEMICAL NAME :: 9,10-Secoergosta-5,7,10(19),22-tetraene-1,3-diol, (1-alpha,3-beta,5Z,7E,22E)-

CAS REGISTRY NUMBER :: 54573-75-0

LAST UPDATED :: 199612

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C28-H44-O2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3500 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 178,432,1985 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 560 ug/kg/4W-I

TOXIC EFFECTS :: Nutritional and Gross Metabolic - changes in calcium Related to Chronic Data - death

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 178,432,1985

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度骨化醇安全信息

[ 符号 ]:

GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H300

[ 警示性声明 ]:
P264-P301 + P310

[ 危害码 (欧洲) ]:
T+

[ 风险声明 (欧洲) ]:
28

[ 安全声明 (欧洲) ]:
28-36/37-45

[ 危险品运输编码 ]:
UN 2811 6.1 / PGIII

度骨化醇合成路线

详细合成路线

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度骨化醇上游产品

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度骨化醇文献

Calcium regulates FGF-23 expression in bone.

Endocrinology 154(12) , 4469-82, (2013)

Calcium has recently been shown to regulate fibroblast growth factor 23 (FGF-23), a bone-derived phosphate and vitamin D-regulating hormone. To better understand the regulation of FGF-23 by calcium, p...

Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study.

Clin. J. Am. Soc. Nephrol. 10(1) , 98-109, (2015)

Elevated parathyroid hormone levels may be associated with adverse clinical outcomes in patients on dialysis. After the introduction of practice guidelines suggesting higher parathyroid hormone target...

A new look at the most successful prodrugs for active vitamin D (D hormone): alfacalcidol and doxercalciferol.

Molecules 14(10) , 3869-80, (2009)

Alfacalcidol (1alpha-hydroxyvitamin D(3)) has been widely used since 1981 as a prodrug for calcitriol (1alpha,25-dihydroxyvitamin D(3)) in the treatment of hypocalcemia, chronic renal failure, hypopar...

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