艾屈肝素钠(Idraparinux Sodium) - 药物靶点：factor Xa_专利_临床

概要

基本信息

药物类型

化学药

别名

Idraparinux、Idraparinux sodium (USAN)、艾卓肝素

+ [6]

靶点

factor Xa

作用机制

factor Xa抑制剂(激活型凝血因子X抑制剂)

治疗领域

心血管疾病呼吸系统疾病

在研适应症-

非在研适应症

心房颤动肺栓塞静脉血栓栓塞+ [1]

原研机构

Sanofi

在研机构-

非在研机构

Sanofi

最高研发阶段无进展临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C38H64NaO49S7

InChIKeyLRWRCXOPMFQZNL-QIEZGXCVSA-N

CAS号149920-56-9

关联

2

项与艾屈肝素钠相关的临床试验

NCT00062803 / Completed临床3期

The Van Gogh-PE Trial, a Multicenter, International, Randomized, Open-Label, Assessor-Blind, Non-Inferiority Study Comparing the Efficacy and Safety of Once-Weekly Subcutaneous SR34006 With the Combination of (LMW)Heparin and Vitamin K Antagonist (VKA) in the Treatment of Acute Symptomatic Pulmonary Embolism

Patients who have a pulmonary embolism (blood clot in the lung) will be treated in this study. The purpose of the study is to compare the safety and effectiveness of a new injectable anticoagulant (blood-thinning) drug, SR34006, with the standard way of treating a pulmonary embolism. The standard treatment includes injections or infusions of an anticoagulant drug, (LMW)heparin, for about a week followed by anticoagulant tablets (warfarin or acenocoumarol) which are taken by mouth.
Assignment to either SR34006 or (LMW)heparin plus warfarin or acenocoumarol will be purely by chance and will be known by both patients and their doctors.

开始日期2003-06-01

申办/合作机构

Sanofi

NCT00067093 / Completed临床3期

Safety and Efficacy Trial Evaluating the Use of SR34006 in the Treatment of Deep Vein Thrombosis (DVT)

Patients who have deep vein thrombosis (blood clot in the leg) will be treated in this study. The purpose of the study is to compare the safety and effectiveness of a new injectable anticoagulant (blood thinning) drug administered once each week, SanOrg34006, with the standard way of treating deep vein thrombosis. The standard treatment includes injections or infusions of an anticoagulant drug (Unfractionated Heparin or low molecular weight heparin) for about a week, followed by vitamin K antagonist (VKA) anticoagulant tablets (warfarin or acenocoumarol) which are taken by mouth. Eligible patients will be assigned to treatment with either SanOrg34006 or the combination of Unfractionated Heparin or low molecular weight heparin plus a VKA (warfarin or acenocoumarol) by random chance. Treatment will be known to both patients and their doctors.

开始日期2003-05-01

申办/合作机构

Sanofi

100 项与艾屈肝素钠相关的临床结果

登录后查看更多信息

100 项与艾屈肝素钠相关的转化医学

登录后查看更多信息

100 项与艾屈肝素钠相关的专利（医药）

登录后查看更多信息

161

项与艾屈肝素钠相关的文献（医药）

2023-04-01·Proteins: Structure, Function, and Bioinformatics

Interactions of heparin derivatives with recombinant human keratinocyte growth factor: Structural stability and bioactivity effect study

Article

作者: Abolhasani, Hoda ; komeili Movahhed, Tahereh ; Kalhor, Reyhaneh ; Rahimi, Hamzeh ; Kalhor, Hourieh

AbstractHeparin and heparan sulfate are important glycosaminoglycans that can regulate the activities of many vital proteins, especially the fibroblast growth factor (FGF) family. Because FGF7 (KGF) has an important role in tissue repair and maintaining the integrity of the mucosal barrier, recombinant human keratinocyte growth factor (rhKGF, palifermin) has been approved for the treatment of wound healing and oral cavity. Due to heparin plays an important role in the KGF signaling pathway, a more detailed study of the drug–drug interactions (DDIs) between rhKGF and heparin at the atomic level and investigating their synergistic effect on each other in terms of biology, especially in silico, is necessary for a better understanding of DDIs. In this study, DDIs between rhKGF and low‐molecular weight heparin types (LMWH) were investigated. In this regard, scrutiny of the influence of the synergistic heparin types on the structure and biostability of rhKGF is accomplished using computational methods such as molecular docking and molecular dynamic simulations (MDs). Subsequently, the motion behavior of rhKGF in interaction with LMWHs was evaluated based on eigenvectors by using principal component analysis (PCA). Also, the binding free energies of rhKGF‐LMWH complexes were calculated by the molecular mechanics/Poisson–Boltzmann surface area (MM‐BPSA) method. The result showed that rhKGF‐idraparinux (−6.9 kcal/mol) and rhKGF‐heparin (−6.0 kcal/mol) complexes had significant binding affinity as well as they had a more stable binding to rhKGF than to other LMWH during 100 ns simulation. However, in order to confirm the curative effect of these drugs, clinical trials must be done.

2022-12-02·The Journal of Organic Chemistry

Synthesis of a Heparinoid Pentasaccharide Containing l-Guluronic Acid Instead of l-Iduronic Acid with Preserved Anticoagulant Activity

Article

作者: Borbás, Anikó ; Kövér, Katalin E. ; Timári, István ; Racskó, Márk ; Bereczky, Zsuzsanna ; Tóth, Balázs István ; Lisztes, Erika ; Herczeg, Mihály ; Demeter, Fruzsina

l-Iduronic acid is a key constituent of heparin and heparan sulfate polysaccharides due to its unique conformational plasticity, which facilitates the binding of polysaccharides to proteins. At the same time, this is the synthetically most challenging unit of heparinoid oligosaccharides; therefore, there is a high demand for its replacement with a more easily accessible sugar unit. In the case of idraparinux, an excellent anticoagulant heparinoid pentasaccharide, we demonstrated that l-iduronic acid can be replaced by an easier-to-produce l-sugar while maintaining its essential biological activity. From the inexpensive d-mannose, through a highly functionalized phenylthio mannoside, the l-gulose donor was prepared by C-5 epimerization in 10 steps with excellent yield. This unit was incorporated into the pentasaccharide by α-selective glycosylation and oxidized to l-guluronic acid. The complete synthesis required only 36 steps, with 21 steps for the longest linear route. The guluronate containing pentasaccharide inhibited coagulation factor Xa by 50% relative to the parent compound, representing an excellent anticoagulant activity. To the best of our knowledge, this is the first biologically active heparinoid anticoagulant which contains a different sugar unit instead of l-iduronic acid.

2021-06-28·Journal of Chemical Information and Modeling2区 · 化学

Conformational Analysis of Heparin-Analogue Pentasaccharides by Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulations

2区 · 化学

Article

作者: Borbás, Anikó ; Kövér, Katalin E. ; Balogh, Gábor ; Herczeg, Mihály ; Sadiq, S. Kashif ; Fehér, Krisztina ; Gyöngyösi, Tamás ; Timári, István

Elucidation and improvement of the blood coagulant properties of heparin are the focus of intense research. In this study, we performed conformational analysis using nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations on the heparin pentasaccharide analogue idraparinux, its disulfonatomethyl analogue, which features a slightly improved blood coagulation property, and a trisulfonatomethyl analogue, in which the activity has been totally abolished. As the ring conformation of the G subunit has been suggested as a major determinant of the biological properties, we analyzed the sugar ring conformations and dynamics of the interglycosidic linkages. We found that the conformation of the G ring is dominated by the ²S_O skewed boat next to the ¹C₄ chair in all three derivatives. Both the thermodynamics and the kinetics of the conformational states were found to be highly similar in the three derivatives. Molecular kinetic analysis showed that the ²S_O skewed boat state of the G ring is equally favorable in the three analogues, resulting in similar ²S_O populations. Also, the transition kinetics from the ¹C₄ chair to the ²S_O skewed boat was found to be comparable in the derivatives, which indicates a similar energy barrier between the two states of the G subunit. We also identified a slower conformational transition between the dominant ⁴C₁ chair and the boat conformations on the E subunit. Both G and E ring flips are also accompanied by changes along the interglycosidic linkages, which take place highly synchronously with the ring flips. These findings indicate that conformational plasticity of the G ring and the dominance of the ²S_O skewed boat populations do not necessarily warrant the biological activity of the derivatives and hence the impact of other factors also needs to be considered.

100 项与艾屈肝素钠相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D10471	艾屈肝素钠	-	DB06406

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
肺栓塞	临床3期	西班牙	Sanofi	2003-06-01
肺栓塞	临床3期	瑞士	Sanofi	2003-06-01
肺栓塞	临床3期	芬兰	Sanofi	2003-06-01
肺栓塞	临床3期	巴西	Sanofi	2003-06-01
肺栓塞	临床3期	阿根廷	Sanofi	2003-06-01
肺栓塞	临床3期	瑞典	Sanofi	2003-06-01
肺栓塞	临床3期	加拿大	Sanofi	2003-06-01
肺栓塞	临床3期	美国	Sanofi	2003-06-01
肺栓塞	临床3期	丹麦	Sanofi	2003-06-01
静脉血栓形成	临床3期	美国	Sanofi	2003-05-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00311090 (EQUINOX, Pubmed \| Br J Clin Pharmacol)	临床1期	静脉血栓形成	757	idrabiotaparinux	繭糧壓夢獵鑰築鹽醖構(壓選壓襯窪繭積鬱蓋顧): ratio estimate = 0.95 (90% CI, 0.87 ~ 1.04) 更多	-	2013-05-01
				idraparinux
NCT00311090 (Pubmed \| J Thromb Haemost)	临床3期	静脉血栓形成	757	Idrabiotaparinux (3 mg)	繭艱顧壓鏇鏇淵網艱醖(製衊觸憲齋壓醖遞醖廠) = 醖醖膚簾蓋獵夢衊構簾淵簾觸觸築獵蓋範製鬱 (夢顧餘簾夢齋鏇膚築觸 ) 更多	-	2011-01-01
				Idraparinux (2.5 mg)	繭艱顧壓鏇鏇淵網艱醖(製衊觸憲齋壓醖遞醖廠) = 願築願蓋顧醖糧壓獵遞淵簾觸觸築獵蓋範製鬱 (夢顧餘簾夢齋鏇膚築觸 ) 更多
Pubmed \| Br Dent J	N/A	静脉血栓栓塞	-	Idraparinux	鑰繭簾蓋鹹鬱觸範憲獵(繭膚窪獵繭廠廠鏇顧膚) = 顧憲鹽衊遞遞鹽鹹鏇憲獵窪齋壓鹽鏇簾壓鏇壓 (獵襯鬱遞遞鹽網壓鑰糧 ) 更多	-	2007-09-13
				Standard therapy	鑰繭簾蓋鹹鬱觸範憲獵(繭膚窪獵繭廠廠鏇顧膚) = 糧憲觸鹽壓廠廠鏇襯餘獵窪齋壓鹽鏇簾壓鏇壓 (獵襯鬱遞遞鹽網壓鑰糧 ) 更多