Sitaxsentan
(Synonyms: N-(4-氯-3-甲基-5-异恶唑基)-2-[(2-甲基-4,5-亚甲二氧基苯基)乙酰]噻吩-3-磺酰胺,IPI 1040; TBC-11251) 目录号 : GC37644
Sitaxsentan (IPI 1040; TBC-11251) 是选择性内皮素A (ETA) 受体拮抗剂。
Cas No.:184036-34-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sitaxsentan (IPI 1040; TBC-11251) is a selective endothelin A (ETA) receptor antagonist. Antihypertensive. Sitaxsentan is used in treatment of chronic heart failure.IC50 value:Target: ETA receptor
[1]. Chin M, Levy RD, Yoshida EM, Byrne MF.Sitaxsentan-induced acute severe hepatitis treated with glucocorticoid therapy.Can Respir J. 2012 Jan-Feb;19(1):e1-2. [2]. Sandoval J, et al. STRIDE-4 investigators.Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension.Pulm Pharmacol Ther. 2012 Feb;25(1):33-9. Epub 2011 Nov 2. [3]. Safdar Z. Effect of transition from sitaxsentan to ambrisentan in pulmonary arterial hypertension.Vasc Health Risk Manag. 2011;7:119-24. Epub 2011 Mar 2. [4]. Rondelet B, et al. Sildenafil added to sitaxsentan in overcirculation-induced pulmonary arterial hypertension.Am J Physiol Heart Circ Physiol. 2010 Oct;299(4):H1118-23. Epub 2010 Aug 6. [5]. Kaehler, et al. Successful treatment of portopulmonary hypertension with the selective endothelin receptor antagonist Sitaxentan. Wien Klin Wochenschr. 2011 Apr;123(7-8):248-52. Epub 2011 Mar 31.
| Cas No. | 184036-34-8 | SDF | |
| 别名 | N-(4-氯-3-甲基-5-异恶唑基)-2-[(2-甲基-4,5-亚甲二氧基苯基)乙酰]噻吩-3-磺酰胺,IPI 1040; TBC-11251 | ||
| Canonical SMILES | O=S(C1=C(C(CC2=CC3=C(C=C2C)OCO3)=O)SC=C1)(NC4=C(C(C)=NO4)Cl)=O | ||
| 分子式 | C18H15ClN2O6S2 | 分子量 | 454.9 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1983 mL | 10.9914 mL | 21.9829 mL |
| 5 mM | 0.4397 mL | 2.1983 mL | 4.3966 mL |
| 10 mM | 0.2198 mL | 1.0991 mL | 2.1983 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Sitaxsentan in the management of pulmonary arterial hypertension
Am J Health Syst Pharm 2007 Feb 15;64(4):363-8.PMID:17299175DOI:10.2146/ajhp060357.
Purpose: The pharmacology, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosing and administration of the endothelin receptor antagonist, Sitaxsentan, and its role in the treatment of pulmonary arterial hypertension (PAH) are reviewed. Summary: PAH is a serious and potentially devastating chronic disorder of the pulmonary circulation. Bosentan is the first and only approved endothelin receptor antagonist for the treatment of PAH. Endothelin-1, a potent endogenous vasoconstrictor and smooth-muscle mitogen, has been shown to be overexpressed in the plasma and lung tissue of patients with PAH; the reduction or blockade of entothelin-1 may aid in disease symptomatology and progression. Activation of ET(A) leads to vasoconstriction and vascular smooth-muscle-cell proliferation. Sitaxsentan is an orally active, organic nonpeptide that binds competitively to the ET(A) receptor. Sitaxsentan, unlike bosentan, has a high affinity for the ET(A) receptor. In one trial, Sitaxsentan was compared with placebo, and the results suggested that Sitaxsentan was more effective than placebo. A 12-week, open-label trial demonstrated the safety and efficacy of Sitaxsentan in 20 patients. The Sitaxsentan to Relieve Impaired Exercise (STRIDE-1) trial randomized patients to receive placebo, Sitaxsentan 100 mg orally once daily, or Sitaxsentan 300 mg orally once daily. Significant improvements in exercise capacity and cardiopulmonary hemodynamics were demonstrated. The results of STRIDE-2, the second randomized Sitaxsentan trial, demonstrated the efficacy and safety of 100 mg Sitaxsentan and the unacceptable safety profile of 300 mg Sitaxsentan. Conclusion: Sitaxsentan is an orally administered endothelin receptor blocker that offers the effective and safe treatment of patients with mild to moderate PAH.
Sitaxsentan for treatment of pulmonary hypertension
Ann Pharmacother 2007 Jan;41(1):100-5.PMID:17164394DOI:10.1345/aph.1G254.
Objective: To review the literature pertinent to the efficacy and safety of Sitaxsentan, a selective endothelin (ET)-A receptor antagonist under evaluation for the treatment of pulmonary arterial hypertension (PAH). Data sources: Articles were identified through searches of the MEDLINE (1966-November 2006) and International Pharmaceutical Abstracts (1970-November 2006) databases, using the key words endothelin antagonist, pulmonary arterial hypertension, pulmonary hypertension, Sitaxsentan, and TBC11251. Searches were limited to articles published in English. Study selection and data extraction: Due to the limited number of articles on Sitaxsentan, all studies captured in the search results were evaluated. Data synthesis: Four studies of Sitaxsentan in humans with PAH have been published to date. An uncontrolled open-label study and a randomized placebo-controlled study (STRIDE-1; Sitaxsentan to Relieve Impaired Exercise-1) showed Sitaxsentan to improve exercise tolerance in patients with PAH, as evidenced by significant increases in the distance walked in 6 minutes. Significant hepatotoxicity developed in patients receiving Sitaxsentan 300 mg. The benefits of Sitaxsentan with respect to exercise tolerance and hemodynamics were sustained in a one year extension of the placebo-controlled study. The results of a multicenter, randomized, placebo-controlled trial of 2 doses of Sitaxsentan with an open-label bosentan arm (STRIDE-2) suggested that only the 100 mg dose provided superior benefit in exercise tolerance and improvement in functional class. Treatment-related adverse effects were similar for all groups. Conclusions: Sitaxsentan appears to be superior to placebo in improving exercise tolerance in patients with PAH but may produce therapeutic outcomes similar to those of bosentan, a comparator agent. The optimal dose of Sitaxsentan appears to be 100 mg once daily. Information about the use of Sitaxsentan in a greater number of patients with PAH for longer periods is necessary to further define its place in the treatment of PAH.
Sitaxsentan: a selective endothelin-A receptor antagonist, for the treatment of pulmonary arterial hypertension
Expert Opin Pharmacother 2007 Jan;8(1):95-109.PMID:17163810DOI:10.1517/14656566.8.1.95.
Pulmonary arterial hypertension (PAH) is a progressive, life-threatening condition. Sitaxsentan, a selective endothelin-A receptor antagonist, is an effective, safe and well-tolerated endothelin receptor antagonist for the treatment of PAH in adult patients. Multi-center, randomized, placebo-controlled clinical trials have demonstrated that Sitaxsentan has beneficial effects on exercise capacity (i.e., 6-min walk distance), functional class and hemodynamic parameters in PAH patients. Sitaxsentan has a low incidence of acute hepatotoxicity. Patients on concomitant warfarin require a decrease in warfarin dose to maintain a therapeutic international normalized ratio. The demonstration of clinical efficacy and low incidence of acute hepatotoxicity support the potential use of Sitaxsentan for the treatment of PAH.
Sitaxsentan sodium for pulmonary hypertension
Drugs Today (Barc) 2008 Aug;44(8):585-600.PMID:18846270DOI:10.1358/dot.2008.44.8.1239808.
Sitaxsentan is the first oral endothelin receptor antagonist (ETRA) with high selectivity for the endothelin-A (ET(A)) receptor to be approved for clinical use by regulatory agencies in Europe for the treatment of pulmonary arterial hypertension (PAH). Clinical trials have shown it to be well tolerated and to improve exercise tolerance, functional class and pulmonary hemodynamics in PAH, results which appear to be at least as good as those for the mixed ETRA bosentan. Importantly, compared to bosentan, Sitaxsentan has a lower incidence of liver toxicity and no interaction with sildenafil, a drug commonly used in the management of PAH. Furthermore, there is increasing evidence to suggest that ETRAs may play an important role in the future management of a wide variety of other conditions, from hypertension and renal disease to connective tissue disease and cancer. In some of these conditions, ET(A) selectivity may be an advantage.
Sitaxsentan: a novel endothelin-A receptor antagonist for pulmonary arterial hypertension
Expert Rev Cardiovasc Ther 2005 Nov;3(6):985-91.PMID:16292989DOI:10.1586/14779072.3.6.985.
Sitaxsentan is an orally active, selective endothelin-A receptor antagonist that may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictive effects of endothelin-A receptors, while maintaining the vasodilator and endothelin-1 clearance functions of the endothelin-B receptors. In its first randomized, placebo-controlled study, Sitaxsentan improved exercise capacity assessed by the 6-min walk test, New York Heart Association functional class, cardiac index and pulmonary vascular resistance in New York Heart Association Class II, III and IV patients with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension related to connective tissue disease or congenital heart disease. Although doses of 100 and 300 mg once daily demonstrated equivalent efficacy, the lower dose had a better safety profile. Additional studies are ongoing to assess the relative safety and efficacy of 50 and 100 mg once-daily dosing. The most common side effects include rhinitis, headache, peripheral edema, chest pain, nausea, constipation, increased prothrombin time/international normalized ratio (in patients on warfarin), flushing and insomnia. As with other endothelin receptor antagonists, increases in hepatic transaminases have been observed with Sitaxsentan. Initial studies using the selective oral endothelin-A receptor antagonist Sitaxsentan in pulmonary arterial hypertension patients have revealed a favorable risk-benefit therapeutic profile with the 100 mg once-daily dose.