AZD6564(AZD6564) - 药物靶点：纤溶酶_在研适应症：出血_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

纤溶酶

作用机制

纤溶酶抑制剂

治疗领域

其他疾病

在研适应症

出血

非在研适应症-

原研机构

AstraZeneca PLC

在研机构

AstraZeneca PLC

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C13H22N2O2

InChIKeyORLPPUHANSFJCS-VHSXEESVSA-N

CAS号1251841-50-5

关联

100 项与 AZD6564 相关的临床结果

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100 项与 AZD6564 相关的转化医学

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100 项与 AZD6564 相关的专利（医药）

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1

项与 AZD6564 相关的文献（医药）

2018-08-01·Neuroscience Letters4区 · 医学

Plasminogen binding inhibitors demonstrate unwanted activities on GABA A and glycine receptors in human iPSC derived neurons

4区 · 医学

Article

作者: Gustafsson, David ; Kristensson, Lisbeth ; Louise Delsing ; Fex, Tomas ; Lundin, Anders ; Ryberg, Erik ; Delsing, Louise ; Fryklund, Jan

Plasminogen binding inhibitors (PBIs) reduce the risk of bleeding in hemorrhagic conditions. However, generic PBIs are also associated with an increased risk of seizures, an adverse effect linked to unwanted activities towards inhibitory neuronal receptors. Development of novel PBIs serve to remove compounds with such properties, but progress is limited by a lack of higher throughput methods with human translatability. Herein we apply human induced pluripotent stem cell (hiPSC) derived neurons in combination with dynamic mass redistribution (DMR) technology to demonstrate robust and reproducible modulation of both GABA_A and glycine receptors. These cells respond to GABA (EC₅₀ 0.33 ± 0.18 μM), glycine (EC₅₀ 11.0 ± 3.7 μM) and additional ligands in line with previous reports from patch clamp technologies. Additionally, we identify and characterize a competitive antagonistic behavior of the prototype inhibitor and drug tranexamic acid (TXA). Finally, we demonstrate proof of concept for effective counter-screening of lead series compounds towards unwanted GABA_A receptor activities. No activity was observed for a previously identified PBI candidate drug, AZD6564, whereas a discontinued analog, AZ13267257, could be characterized as a potent GABA_A receptor agonist.

100 项与 AZD6564 相关的药物交易

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