HUP-55(HUP-55) - 药物靶点：PREP_在研适应症：帕金森病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

PREP

作用机制

PREP抑制剂(脯氨酰内肽酶抑制剂)

治疗领域

神经系统疾病内分泌与代谢疾病

在研适应症

帕金森病

非在研适应症-

原研机构

University of Helsinki

在研机构

University of Helsinki

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C18H21N3O

InChIKeyFEEUIAMWBWZZNX-INIZCTEOSA-N

CAS号-

关联

100 项与 HUP-55 相关的临床结果

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100 项与 HUP-55 相关的转化医学

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100 项与 HUP-55 相关的专利（医药）

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1

项与 HUP-55 相关的文献（医药）

2023-06-08·Journal of medicinal chemistry1区 · 医学

Nonpeptidic Oxazole-Based Prolyl Oligopeptidase Ligands with Disease-Modifying Effects on α-Synuclein Mouse Models of Parkinson's Disease.

1区 · 医学

Article

作者: Svarcbahs, Reinis ; Myöhänen, Timo T ; Kilpeläinen, Tommi P ; Auno, Samuli ; Leino, Teppo O ; Jäntti, Maria ; Sipari, Nina ; Wallén, Erik A A ; Eteläinen, Tony S ; Pätsi, Henri T ; Norrbacka, Susanna ; Cui, Hengjing ; Julku, Ulrika H

Prolyl oligopeptidase (PREP) is a widely distributed serine protease in the human body cleaving proline-containing peptides; however, recent studies suggest that its effects on pathogenic processes underlying neurodegeneration are derived from direct protein-protein interactions (PPIs) and not from its regulation of certain neuropeptide levels. We discovered novel nonpeptidic oxazole-based PREP inhibitors, which deviate from the known structure-activity relationship for PREP inhibitors. These new compounds are effective modulators of the PPIs of PREP, reducing α-synuclein (αSyn) dimerization and enhancing protein phosphatase 2A activity in a concentration-response manner, as well as reducing reactive oxygen species production. From the best performing oxazoles, HUP-55 was selected for in vivo studies. Its brain penetration was evaluated, and it was tested in αSyn virus vector-based and αSyn transgenic mouse models of Parkinson's disease, where it restored motor impairment and reduced levels of oligomerized αSyn in the striatum and substantia nigra.

100 项与 HUP-55 相关的药物交易

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