This is a Phase 2, multicenter, open-label, single-arm, sequential cohort study to be conducted in up to 30 subjects. The study will evaluate subjects undergoing primary, elective, off-pump CABG surgery with median sternotomy.

开始日期2013-01-01

申办/合作机构

ARCA biopharma, Inc.

100 项与 NU-172 相关的临床结果

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100 项与 NU-172 相关的转化医学

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100 项与 NU-172 相关的专利（医药）

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项与 NU-172 相关的文献（医药）

2021-06-01·International Journal of Biological Macromolecules1区 · 化学

Structural and functional analysis of the simultaneous binding of two duplex/quadruplex aptamers to human α-thrombin

1区 · 化学

Article

作者: Santamaria, Andreas ; Troisi, Romualdo ; Balasco, Nicole ; Sica, Filomena ; Vitagliano, Luigi

The long-range communication between the two exosites of human α-thrombin (thrombin) tightly modulates the protein-effector interactions. Duplex/quadruplex aptamers represent an emerging class of very effective binders of thrombin. Among them, NU172 and HD22 aptamers are at the forefront of exosite I and II recognition, respectively. The present study investigates the simultaneous binding of these two aptamers by combining a structural and dynamics approach. The crystal structure of the ternary complex formed by the thrombin with NU172 and HD22_27mer provides a detailed view of the simultaneous binding of these aptamers to the protein, inspiring the design of novel bivalent thrombin inhibitors. The crystal structure represents the starting model for molecular dynamics studies, which point out the cooperation between the binding at the two exosites. In particular, the binding of an aptamer to its exosite reduces the intrinsic flexibility of the other exosite, that preferentially assumes conformations similar to those observed in the bound state, suggesting a predisposition to interact with the other aptamer. This behaviour is reflected in a significant increase of the anticoagulant activity of NU172 when the inactive HD22_27mer is bound to exosite II, providing a clear evidence of the synergic action of the two aptamers.

2020-08-03·Chemistry – A European Journal2区 · 化学

Structure–Activity Relationship Study of a Potent α‐Thrombin Binding Aptamer Incorporating Hexitol Nucleotides

2区 · 化学

Article

作者: Herdewijn, Piet ; Sica, Filomena ; D'Alonzo, Daniele ; Troisi, Romualdo ; Guaragna, Annalisa ; De Fenza, Maria ; Eremeeva, Elena ; Yang, Hui ; Esposito, Anna

AbstractThe replacement of one or more nucleotide residues in the potent α‐thrombin‐binding aptamer NU172 with hexitol‐based nucleotides has been devised to study the effect of these substitutions on the physicochemical and functional properties of the anticoagulant agent. The incorporation of single hexitol nucleotides at the T9 and G18 positions of NU172 substantially retained the physicochemical features of the parent oligonucleotide, as a result of the biomimetic properties of the hexitol backbone. Importantly, the NU172‐TH9 mutant exhibited a higher binding affinity toward human α‐thrombin than the native aptamer and an improved stability even after 24 h in 90 % human serum, with a significant increase in the estimated half‐life. The anticoagulant activity of the modified oligonucleotide was also found to be slightly preferable to NU172. Overall, these results confirm the potential of hexitol nucleotides as biomimetic agents, while laying the foundations for the development of NU172‐inspired α‐thrombin‐binding aptamers.

2020-03-01·FEBS Letters

Exploring the efficiency of thrombin inhibitors with a quantitative model of the coagulation cascade

Article

作者: Kopylov, Alexey M. ; Zavyalova, Elena G. ; Ustinov, Nikita B.

A detailed mathematical description of the coagulation cascade is a challenging task due to a huge set of protein–protein interactions. Simplified models do not permit quantitative description of anticoagulants. The detailed mathematical model presented here was constructed with 98 reactions between 70 species. The model was verified using experimental data on thrombin generation. Four thrombin inhibitors, which have different inhibitory mechanisms, were incorporated into the model. All four thrombin inhibitors delayed prothrombin conversion into thrombin, but did not preclude it. At high inhibitor concentration, thrombin‐mediated positive feedback loops were strongly inhibited and the proportion of prothrombin, converted with factor Xa only, was considerably increased. The most potent inhibitor of prothrombin conversion was aptamer NU172, which also binds prothrombin and inhibits its conversion.

100 项与 NU-172 相关的药物交易

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