Azilsartan/阿齐沙坦 {[allProObj[0].p_purity_real_show]}

Azilsartan/阿齐沙坦 质控信息

Azilsartan/阿齐沙坦 生物活性

靶点

AT1 receptor AT1 receptor, IC50:2.6 nM

描述

The numerous effects of Angiotensin II (AII), including its roles in vasoconstriction, secretion of aldosterone and vasopressin, cellular proliferation, and hypertrophy are dominantly mediated through the activation of the angiotensin type 1 (AT1) receptor, a member of the superfamily of G protein-coupled receptors. Azilsartan (AZL) is an AT1 receptor antagonist with IC50 of 2.6 nM. Pretreatment of AZL for 90 min inhibited the specific binding of 125I-Sar1-Ile8-AII to human AT1 receptors expressed in CHO cells in a concentration-related manner with an IC50 of 2.6 nM, indicating a high affinity for AT1 receptors. A potent inhibitory effect of AZL at AT1 receptors was maintained even 5 h after washout with an IC50 value of 7.4 nM. Pretreatment of intact COS-7 cells expressing human AT1 receptor with AZL for 2 h inhibited the accumulation of IP1 with IC50 value of 9.2 nM. Pretreatment with 0.1, 0.3, or 1 nM AZL for 30 min inhibited AII-induced aortic contraction in a concentration-related manner [7].

Azilsartan/阿齐沙坦 细胞实验

Cell Line Osteoclast precursors Osteoblasts Macrophages Bone marrow-derived monocytes/macrophages (BMMs) BEnd.3 brain endothelial cells MLO-Y4 cells	Concentration	Treated Time	Description	References
Osteoclast precursors	0, 0.01, 0.1, 1, 10 μM	5 days	To evaluate the effect of Azilsartan on RANKL-induced osteoclastogenesis. Results showed that Azilsartan did not significantly inhibit RANKL-induced osteoclastogenesis.	Front Endocrinol (Lausanne). 2023 Sep 15;14:1207502.
Osteoblasts	1 μM	3 days	To evaluate the effect of Azilsartan on LPS-induced RANKL expression. Results showed that Azilsartan had no significant effect on LPS-induced RANKL mRNA and protein expression.	Front Endocrinol (Lausanne). 2023 Sep 15;14:1207502.
Macrophages	1 μM	3 days	To evaluate the effect of Azilsartan on LPS-induced TNF-α expression. Results showed that Azilsartan significantly reduced TNF-α mRNA and protein levels compared to macrophages treated with LPS alone.	Front Endocrinol (Lausanne). 2023 Sep 15;14:1207502.
Bone marrow-derived monocytes/macrophages (BMMs)	0, 0.25, 0.5, 1 μM	5 days	To evaluate the inhibitory effect of Azilsartan on RANKL-mediated osteoclast differentiation. Results showed that Azilsartan significantly inhibited osteoclast formation and downregulated the expression of osteoclast-associated markers (Nfatc1, c-Fos, Ctsk).	Front Pharmacol. 2021;12:774709.
BEnd.3 brain endothelial cells	3 μM and 6 μM	24 hours	Azilsartan significantly alleviated high glucose-induced endothelial monolayer permeability and decreased occludin expression	Bioengineered. 2021 Dec;12(1):3621-3633.
MLO-Y4 cells	10^-7 M	48 hours	To evaluate the effect of Azilsartan on Ang II-induced RANKL and M-CSF mRNA expression. Results showed that Azilsartan significantly inhibited the upregulation of RANKL and M-CSF mRNA expression induced by Ang II.	Biomedicines. 2025 Feb 10;13(2):426.
展开

Azilsartan/阿齐沙坦 动物实验

Species C57BL6/J mice C57BL/6J mice Male db/db mice Male KKAy diabetic mice	Animal Model LPS-induced inflammatory bone resorption model Ovariectomy (OVX)-induced osteoporosis model Diabetes model Diabetic mouse model	Administration	Dosage	Frequency	Description	References
C57BL6/J mice	LPS-induced inflammatory bone resorption model	Subcutaneous injection	100 µg/day	Once daily for 5 consecutive days	To evaluate the effect of Azilsartan on LPS-induced bone resorption and osteoclastogenesis. Results showed that Azilsartan significantly inhibited LPS-induced bone resorption and osteoclastogenesis, and reduced the mRNA expression levels of TRAP, cathepsin K, RANKL, and TNF-α.	Front Endocrinol (Lausanne). 2023 Sep 15;14:1207502.
C57BL/6J mice	Ovariectomy (OVX)-induced osteoporosis model	Oral gavage	1 mg/kg and 3 mg/kg	Twice a week for 6 weeks	To evaluate the protective effect of Azilsartan on OVX-induced osteoporosis. Results showed that Azilsartan significantly ameliorated OVX-induced bone loss and decreased ROS levels.	Front Pharmacol. 2021;12:774709.
Male db/db mice	Diabetes model		20 μg/day	10 consecutive days	Azilsartan dramatically reversed increased BBB permeability, suppressed occludin expression, excessive release of inflammatory factors, and downregulation of KLF2 in diabetic mice	Bioengineered. 2021 Dec;12(1):3621-3633.
Male KKAy diabetic mice	Diabetic mouse model	Mixed in diet	0.005%	3 weeks	Azilsartan restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser1177/Thr497 of endothelial nitric oxide synthase in diabetic mice	Cardiovasc Diabetol. 2014 Jan 31;13:30
展开

Azilsartan/阿齐沙坦 动物研究

Dose	Mice: 1 mg/kg - 10 mg/kg[3] (p.o.) Rat: 10 mg/kg[4] (p.o.), 0.3 mg/kg - 3 mg/kg[5] (p.o.)
Administration	p.o.
Pharmacokinetics	Animal Rats[6] Dogs[6] Monkeys[6] Dose 1 mg/kg (p.o.) 0.2 mg/kg (i.v.) 1 mg/kg (p.o.) 0.2 mg/kg (i.v.) 3 mg/kg (p.o., fasted) 0.2 mg/kg (i.v., fasted) Administration p.o. i.v. p.o. i.v. p.o. i.v. F 14.6% (p.o.) 24.3% (p.o.) 13.6% (p.o.) AUC0→24h 7.26 μg·h/ml (p.o.) 9.97 μg·h/ml (i.v.) 1.18 μg·h/ml (p.o.) 0.97 μg·h/ml (i.v.) 6.71 μg·h/ml (p.o.) 3.36 μg·h/ml (i.v.) T1/2 5.2 h (p.o.) 2.9 h (p.o.) 1.4 h (p.o.) 1.6 h (i.v.) Tmax 1.7 h (p.o.) 0.8 h (p.o.) 1.7 h (p.o.) Cmax 0.901 μg/ml (p.o.) 0.247 μg/ml (p.o.) 0.264 μg/ml (p.o.) 3.637 μg/ml (i.v.)

Azilsartan/阿齐沙坦 临床研究

NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
NCT01715584	Hypertension	Phase 4	Recruiting	December 31, 2019	Canada, Ontario ... 展开 >> London Health Sciences Centre - Victoria Campus Recruiting London, Ontario, Canada, N6A 5W9 Contact: Craig J Railton, MD, PhD    519 685 8500 ext 58525    Craig.Railton@lhsc.on.ca    Principal Investigator: Craig J Railton, MD, PhD          Sub-Investigator: Jonathan Fairbairn, BSc          Sub-Investigator: George Nicoloau, MD          Sub-Investigator: Robert Gros, PhD          Sub-Investigator: Jason Franklin, MD          Sub-Investigator: John Yoo, MD          Sub-Investigator: Kevin Fung, MD          Sub-Investigator: Anthony Nichols, MD          Sub-Investigator: Danielle McNeil, MD 收起 <<
NCT02235909	Hypertension	Phase 3	Recruiting	August 2020	-
NCT00362115	Hypertension	Phase 2	Completed	-	-
展开

Azilsartan/阿齐沙坦 参考文献

Azilsartan/阿齐沙坦 实验方案

计算器	摩尔计算器 总药量计算器 工作液计算器
存储液制备		1mg	5mg	10mg
	1 mM 5 mM 10 mM	2.19mL 0.44mL 0.22mL	10.95mL 2.19mL 1.10mL	21.91mL 4.38mL 2.19mL

Azilsartan/阿齐沙坦 技术信息