LEI-301(LEI-301) - 药物靶点：PLAAT_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

PLAAT

作用机制

PLAAT 抑制剂(Phospholipase A and acyltransferase family inhibitors)

治疗领域-

在研适应症-

非在研适应症-

原研机构

University of Leiden

在研机构

Academisch Ziekenhuis Leiden

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-

关联

100 项与 LEI-301 相关的临床结果

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100 项与 LEI-301 相关的转化医学

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100 项与 LEI-301 相关的专利（医药）

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1

项与 LEI-301 相关的文献（医药）

2020-09-10·Journal of Medicinal Chemistry1区 · 医学

Structure–Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family

1区 · 医学

Article

作者: van der Stelt, Mario ; Stevens, Anna F. ; Wendel, Tiemen J. ; Jiang, Ming ; Tran, Yvonne ; Mock, Elliot D. ; Kantae, Vasudev ; Mohr, Florian ; van Westen, Gerard J.P. ; van der Wel, Tom ; de Koster, Nicky ; Hankemeier, Thomas ; Di, Xinyu ; Ofman, Tim P. ; Al Ayed, Karol ; Burggraaff, Lindsey ; Zhou, Juan ; Martella, Andrea

The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca²⁺-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiological processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified α-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the α-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301, a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiological role of the PLAATs.

100 项与 LEI-301 相关的药物交易

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