Candesartan is an oral blocker of AngII type-1 receptors (AT1R), with an IC50 value of 0.26nM[1]. Candesartan can inhibit the viral activity of SARS-CoV-2 with an IC50 value of 5.944μM[2]. Candesartan has been widely used to inhibit renal vasoconstriction in rodents, blocking AT1A and AT1B receptors in rodent renal resistance vessels[3].
In vitro, Candesartan treatment at 20µM for 24h significantly induced apoptosis and inhibited cell migration in CT-26 and SW-480 cells [4]. Treatment of human embryonic kidney epithelial cells with 100μM Candesartan for 24h significantly reduced TNF-α-induced TGF-β and IL-6 expression and blocked TNF-α-induced ROS activation[5]. Treatment with 1μM Candesartan for 48h specifically reversed the AngII-induced decrease in miR-301b levels in rat aortic smooth muscle cells (RASMCs) and significantly reduced the AngII-induced increase in STAT3 expression[6].
In vivo, Candesartan treatment via oral administration at a dose of 2mg/kg/day for 28 days significantly reduced tumor volume and inhibited tumor angiogenesis in the murine xenograft model of bladder cancer[7]. Intraperitoneal administration of Candesartan (10mg/kg/day) for 7 days significantly reduced pathological neovascularization and improved capillary perfusion in a mouse model of ischemic retinopathy[8]. Oral administration of Candesartan at a dose of 1mg/kg/day for 21 days significantly improved insulin resistance, hepatic steatosis, and dyslipidemia in the high-fat diet (HFD)-fed mice[9].
References:
[1] Abreu Diaz A M, Drumeva G O, Petrenyov D R, et al. Synthesis of the novel AT1 receptor tracer [18F] fluoropyridine–candesartan via click chemistry[J]. Acs Omega, 2020, 5(32): 20353-20362.
[2] Alnajjar R, Mostafa A, Kandeil A, et al. Molecular docking, molecular dynamics, and in vitro studies reveal the potential of angiotensin II receptor blockers to inhibit the COVID-19 main protease[J]. Heliyon, 2020, 6(12).
[3] Ruan X, Purdy K E, Oliverio M I, et al. Effects of candesartan on angiotensin II-induced renal vasoconstriction in rats and mice[J]. Journal of the American Society of Nephrology: JASN, 1999, 10: S202-7.
[4] Tabatabai E, Khazaei M, Asgharzadeh F, et al. Inhibition of angiotensin II type 1 receptor by candesartan reduces tumor growth and ameliorates fibrosis in colorectal cancer[J]. Excli Journal, 2021, 20: 863.
[5] Yu Y, Jiang H, Niu Y, et al. Candesartan inhibits inflammation through an angiotensin II type 1 receptor independent way in human embryonic kidney epithelial cells[J]. Anais da Academia Brasileira de Ciências, 2019, 91(02): e20180699.
[6] Zhang L, Yang F, Yan Q. Candesartan ameliorates vascular smooth muscle cell proliferation via regulating miR-301b/STAT3 axis[J]. Human Cell, 2020, 33(3): 528-536.
[7] Kosugi M, Miyajima A, Kikuchi E, et al. Angiotensin II type 1 receptor antagonist candesartan as an angiogenic inhibitor in a xenograft model of bladder cancer[J]. Clinical cancer research, 2006, 12(9): 2888-2893.
[8] Shanab A Y, Elshaer S L, El-Azab M F, et al. Candesartan stimulates reparative angiogenesis in ischemic retinopathy model: role of hemeoxygenase-1 (HO-1)[J]. Angiogenesis, 2015, 18(2): 137-150.
[9] Lee J W, Gu H O, Jung Y, et al. Candesartan, an angiotensin-II receptor blocker, ameliorates insulin resistance and hepatosteatosis by reducing intracellular calcium overload and lipid accumulation[J]. Experimental & molecular medicine, 2023, 55(5): 910-925.
Candesartan是一种口服血管紧张素II 1型受体（AT1R）阻断剂，IC50值为0.26nM[1]。Candesartan可抑制SARS-CoV-2的病毒活性（IC50=5.944μM）[2]。Candesartan广泛应用于啮齿类动物模型中抑制肾血管收缩，阻断肾阻力血管中的AT1A和AT1B受体[3]。
在体外，20µM的Candesartan处理CT-26和SW-480细胞24小时可显著诱导凋亡并抑制细胞迁移[4]。100μM的Candesartan处理人胚胎肾上皮细胞24小时能降低TNF-α诱导的TGF-β和IL-6表达，并阻断TNF-α引发的ROS激活[5]。1μM的Candesartan处理大鼠主动脉平滑肌细胞（RASMCs）48小时可特异性逆转AngII引起的miR-301b水平下降，并显著抑制AngII诱导的STAT3表达增加[6]。
在体内，膀胱癌异种移植小鼠模型每日口服Candesartan（2mg/kg/day；持续28天）可显著减小肿瘤体积并抑制肿瘤血管生成[7]。缺血性视网膜病变小鼠模型每日腹腔注射10mg/kg剂量的Candesartan（持续7天）能减少病理性新生血管并改善毛细血管灌注[8]。高脂饮食（HFD）小鼠每日口服1mg/kg剂量的Candesartan（持续21天）可显著改善胰岛素抵抗、肝脏脂肪变性和血脂异常[9]。