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Otamixaban

现货
Catalog No.
A3690
因子Xa抑制剂
组合的产品项目
规格价格库存 数量
10mg
¥ 5,140.00
现货
100mg
¥ 12,340.00
现货

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Background

Otamixaban (FXV673) is a potent, selective, rapid acting, competitive and reversible inhibitor of factor Xa with IC50 value of 0.4 nM.[5]
Factor Xa is a serine endopeptidase which is activated into factor Xa by both factor IX with its cofactor, factor VIII known as intrinsic Xase, and factor VII with its cofactor, tissue factor. Factor Xa (fXa) is a pivotal serine protease situated at the juncture of the intrinsic and extrinsic pathways of the blood coagulation cascade.[2] Its singular role in thrombin activation and potentiating effects on clot formation makes it as a target for therapeutic intervention. FXa is responsible for the initiation of the coagulation cascade,[3] cleaving prothrombin to its active form thrombin, which then acts to convert soluble fibrinogen to insoluble fibrin and to activate platelets. Stabilization of the platelet aggregation by fibrin mesh ultimately leads to clot formation.[4] Thus, the inhibition of fXa (in the physiologically relevant prothrombinase complex) represents an attractive target for the development of novel antithrombotic agents.[5]
Otamixaban (FXV673) selectively and competitively inhibit FXa, suppressing prothrombin activity at the sites of blood clot (thrombus) formation. This leads to a decrease in blood clot formation in a dose dependent manner.[1] Reducing blood clot formation will decrease blood flow blockages, thus possibly lowering the risk of myocardial infarction, unstable angina, venous thrombosis, and ischemic stroke.[6] In conclusion, FXV673 is an effective inhibitor of fXa in the physiologically relevant human prothrombinase complex. Recently a new series of specific, direct acting inhibitors of Factor Xa has been developed. And they may be more effective against Factor Xa in that they inhibit both free Factor Xa and Factor Xa in the prothrombinase complex.[7]
References:
1.K. R. Guertin et al. Optimization of the-Aminoester Class of Factor Xa Inhibitors.Part 2: Identification of FXV673 as a Potent and Selective Inhibitor with Excellent In Vivo Anticoagulant Activity. Bioorg. Med. Chem. Lett. 12 (2002) 1671–1674.
2.Meyer-Michel Samama. et al. Monitoring plasma levels of factor Xa inhibitors: how, why and when? Expert Rev. Hematol.2013, 6(2), 155-164.
3.Rebello SS1. et al. Antithrombotic efficacy of a novel factor Xa inhibitor, FXV673, in a canine model of coronary artery thrombolysis. Br J Pharmacol. 2001 Aug;133(7):1190-8.
4.Valeria Chu. et al. Pharmacological Characterization of a Novel Factor Xa Inhibitor, FXV673. Thrombosis Research 103 (2001) 309–324.
5.Katsung, B., S. Masters and A. Trevor. Basic and Clinical Pharmacology 11th Edition. United States of America: McGraw-Hill, 2009.
6.Rebello SS1. et al. Role of short-term inhibition of factor Xa by FXV673 in arterial passivation: a study in a chronic model of thrombosis in conscious dogs. J Cardiovasc Pharmacol. 2001,38(2):288-97.
7.Turpie AG. "Oral, Direct Factor Xa Inhibitors in Development for the Prevention and Treatment of Thromboembolic Diseases". Arterioscler Thromb Vasc Biol,2007,27 (6): 1238-47.

Chemical Properties

StorageStore at -20°C
M.Wt446.53
Cas No.193153-04-7
FormulaC25H26N4O4
SynonymsFXV 673; FXV-673; FXV673
Solubility≥22.35 mg/mL in DMSO, ≥55 mg/mL in EtOH with gentle warming, <2.38 mg/mL in H2O
Chemical Namemethyl (2R,3R)-2-[(3-carbamimidoylphenyl)methyl]-3-[[4-(1-oxidopyridin-1-ium-4-yl)benzoyl]amino]butanoate
SDFDownload SDF
Canonical SMILESCC(C(CC1=CC=CC(=C1)C(=N)N)C(=O)OC)NC(=O)C2=CC=C(C=C2)C3=CC=[N+](C=C3)[O-]
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

体外实验[1]:

样品

衍生自人,灵长类动物,狗,兔和大鼠的血浆

溶解方法

在DMSO中的溶解度>22.4mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

100 ng/mL

应用

Otamixaban在血浆中的抗凝作用为兔子>人类>猴>大鼠>狗。在PT和aPTT实验中,人类对Otamixaban的敏感性比狗高约2.5倍。100 ng / mL将是靶向人类临床研究的有效血浆浓度。

动物实验[1]:

动物模型

氯化亚铁诱导的动脉血栓形成大鼠模型

剂量

50μg/ kg推注;5μg/ kg / min静脉注射维持输液

应用

在氯化亚铁诱发的动脉血栓形成大鼠模型中,Otamixaban剂量依赖性的增加闭塞时间,最大有效剂量为约50μg/ kg推注和5μg/ kg / min静脉维持输液。与对照相比,该剂量导致血栓质量降低40%。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

[1] Guertin KR1, Choi YM. The discovery of the Factor Xa inhibitor otamixaban: from lead identification to clinical development. Curr Med Chem. 2007;14(23):2471-81.

生物活性

描述 Otamixaban(FXV673)是一种有效的、选择性的、速效的、竞争性的和可逆的fXa抑制剂,Ki值为0.5 nM。
靶点 Factor Xa          
IC50 0.5 nM (Ki)          

质量控制

化学结构

Otamixaban