Sitaxentan sodium is a selective endothelin A receptor (ETA) antagonist (IC50 = 1.4 nM; Ki = 0.43nM) [1]. Sitaxentan sodium selectively blocks the action of endothelin (ET) on endothelin A (ETA) receptors [2]. Sitaxentan sodium is often used to treat pulmonary hypertension [3].
In Surgery for wire injury mouse model, Sitaxentan sodium (15mg/kg; po; 28d) inhibits the formation of neointimal lesions in femoral arteries of mice [4]. In rat toxicity experiments, Sitaxentan sodium (10, 30, 60mg/kg; po; 9 weeks) did not affect the survival, clinical symptoms, or body weight of rats [5]. In humanized liver chimeric mice, triglyceride (TG) levels in mice treated with Sitaxentan sodium (10mg/kg; po; single dose) were significantly increased [6].
References:
[1]. Tilton RG, Munsch CL, Sherwood SJ, et al. Attenuation of pulmonary vascular hypertension and cardiac hypertrophy with sitaxsentan sodium, an orally active ETAreceptor antagonist. Pulmonary pharmacology & therapeutics. 2000 Apr 1; 13(2): 87-97.
[2]. Rondelet B, Dewachter L, Kerbaul F, et al. Sildenafil added to sitaxsentan in overcirculation-induced pulmonary arterial hypertension. American Journal of Physiology-Heart and Circulatory Physiology. 2010 Oct;299(4):H1118-H1123.
[3]. Barst RJ, Langleben D, Frost A, et al. Sitaxsentan therapy for pulmonary arterial hypertension. American journal of respiratory and critical care medicine. 2004 Feb 15;169(4):441-447.
[4]. Duthie KM, Hadoke PW, Kirkby NS, et al. Selective endothelin A receptor antagonism with sitaxentan reduces neointimal lesion size in a mouse model of intraluminal injury. British Journal of Pharmacology. 2015 Jun; 172(11): 2827-2837.
[5]. Cross DM, Derzi M, Horsley E, et al. Evaluation of sitaxentan (Thelin®) toxicity in juvenile rats and regulatory interactions during the development of a European Medicines Agency pediatric investigation plan. Regulatory Toxicology and Pharmacology. 2012 Oct 1; 64(1): 43-50.
[6]. King A, Baginski M, Morikawa Y, et al. Application of a novel mass spectral data acquisition approach to lipidomic analysis of liver extracts from sitaxentan-treated liver-humanized PXB mice. Journal of proteome research. 2019 Sep 24; 18(11): 4055-4064.
Sitaxentan sodium是一种选择性内皮素A受体（ETA）拮抗剂（IC50 = 1.4nM；Ki = 0.43nM）[1]。Sitaxentan sodium选择性阻断内皮素（ET）对内皮素A受体（ETA）的作用 [2]。Sitaxentan sodium常用于治疗肺动脉高压 [3]。
在钢丝损伤手术小鼠模型中，Sitaxentan sodium（15mg/kg；po；28d）可抑制小鼠股动脉新生内膜病变的形成 [4]。在大鼠毒性实验中，Sitaxentan sodium（10、30、60mg/kg；po；9周）对大鼠的生存期、临床症状和体重均无影响 [5]。在人源化肝嵌合小鼠中，用Sitaxentan sodium（10mg/kg；po；单剂量）治疗的小鼠的甘油三酯（TG）水平显著升高 [6]。