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Sitaxsentan sodium

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Chemical Structure| 210421-74-2 同义名 : TBC11251 sodium;IPI 1040 sodium;Thelin;TBC 11251;Sitaxentan (sodium salt)
CAS号 : 210421-74-2
货号 : A180363
分子式 : C18H14ClN2NaO6S2
纯度 : 99%+
分子量 : 476.89
MDL号 : MFCD11040990
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(220.18 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 100 mg/mL(209.69 mM)，配合低频超声助溶
动物实验配方：
生物活性
描述 G protein-coupled receptor (GPCR) agonists through their receptors can transactivate protein tyrosine kinase receptors such as epidermal growth factor receptor and serine/threonine kinase receptors most notably transforming growth factor (TGF)-β receptor (TβRI). Several GPCR agonists such as Ang II, thrombin, ET-1 can mediate the transactivation of a multitude of protein tyrosine kinase receptors[3]. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide thought to play a critical role in the pathogenesis and progression of PAH. The biological effects of ET-1 are mediated through the endothelin receptor subtype A (ETA) and endothelin receptor subtype B (ETB). Sitaxsentan Sodium is an ETA-selective endothelin receptor antagonists (ERAs) with IC50 value of 1.4 nM[4]. Patients with New York Heart Association (NYHA) functional class II-IV PAH treated with 100 mg sitaxsentan showed statistically significant improvements in 6-minute walk distance (6MWD) (35 m placebo corrected improvement, p<0.01) and 29% of the sitaxsentan 100-mg patients improved by at least one functional class without any deteriorations[5].
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
NCT00593905 - Unknown July 2013 United States, Pennsylvania ... 展开 >> Allegheny General Hospital Recruiting Pittsburgh, Pennsylvania, United States, 15212 Contact: Andrea L Nowicki, BA    412-359-3653    anowicki@wpahs.org    Contact: Raymond L Benza, MD    412.359.3584    rbenza@wpahs.org    Principal Investigator: Raymond L Benza, MD 收起 <<
NCT00810732 Chronic Kidney Disease ... 展开 >> CRD 收起 << Phase 2 Completed - United Kingdom ... 展开 >> Pfizer Investigational Site Edinburgh, Scotland, United Kingdom, EH4 2XU 收起 <<
NCT00796666 Pulmonary Arterial Hypertensio... 展开 >>n Pulmonary Hypertension 收起 << Phase 3 Terminated(Safety Issue The tr... 展开 >>ial was prematurely terminated on Dec 9, 2010, due to safety concerns, specifically new emerging evidence of hepatic injury.) 收起 << - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.10mL

0.42mL

0.21mL

10.48mL

2.10mL

1.05mL

20.97mL

4.19mL

2.10mL
参考文献

[1]Tilton RG, Munsch CL, et al. Attenuation of pulmonary vascular hypertension and cardiac hypertrophy with sitaxsentan sodium, an orally active ET(A) receptor antagonist. Pulm Pharmacol Ther. 2000;13(2):87-97.

[2]Wu C, Chan MF, et al. Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist. J Med Chem. 1997 May 23;40(11):1690-7.

[3]Sharifat N, Mohammad Zadeh G, Ghaffari MA, Dayati P, Kamato D, Little PJ, Babaahmadi-Rezaei H. Endothelin-1 (ET-1) stimulates carboxy terminal Smad2 phosphorylation in vascular endothelial cells by a mechanism dependent on ET receptors and de novo protein synthesis. J Pharm Pharmacol. 2017 Jan;69(1):66-72. doi: 10.1111/jphp.12654. Epub 2016 Dec 1. PMID: 27905105.

[4]Wu C, Decker ER, Blok N, Li J, Bourgoyne AR, Bui H, Keller KM, Knowles V, Li W, Stavros FD, Holland GW, Brock TA, Dixon RA. Acyl substitution at the ortho position of anilides enhances oral bioavailability of thiophene sulfonamides: TBC3214, an ETA selective endothelin antagonist. J Med Chem. 2001 Apr 12;44(8):1211-6. doi: 10.1021/jm000349x. PMID: 11312921.

[5]Waxman AB. A review of sitaxsentan sodium in patients with pulmonary arterial hypertension. Vasc Health Risk Manag. 2007;3(1):151-7. PMID: 17583185; PMCID: PMC1994033.