更新于：2024-11-01

eNOS x EEF1A1

更新于：2024-11-01

基本信息

关联

项与 eNOS x EEF1A1 相关的药物

Malifutai

吗利福肽

靶点

EEF1A1 x eNOS

作用机制

EEF1A1抑制剂 [+1]

在研机构

八加一药业股份有限公司

原研机构

广东八加一医药有限公司

在研适应症

缺血性卒中 [+1]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 eNOS x EEF1A1 相关的临床试验

CTR20211420 / Completed临床1期

中国健康受试者单次静脉滴注（IV）BJY-801的药代动力学研究

评估中国健康受试者单次静脉滴注（Ⅳ）给药后BJY-801的安全性、耐受性及药代动力学特征。

开始日期2021-07-13

申办/合作机构

广东八加一医药有限公司

[+1]

CTR20202066 / Completed临床1期

中国健康受试者单次静脉滴注BJY-801的耐受性研究

根据非临床研究及已完成临床研究（MLFT-protocol-01）数据分析判断，需进一步探索BJY-801在中国成年健康人体单次给药的安全剂量范围，评估健康人体单次静脉滴注BJY-801的安全性和耐受性，为制定多次耐受和药代动力学研究及Ⅱ期临床试验给药方案提供依据。

开始日期2020-10-22

申办/合作机构

广东八加一医药有限公司

[+1]

CTR20170068 / Completed临床1期

中国健康志愿者单次静滴注射用吗利福肽的耐受性和药代动力学研究临床试验

观察健康人体单次接受滴注注射用吗利福肽的安全性和耐受性，评估注射用吗利福肽在健康人体单次给药的安全剂量范围及其在中国健康人体内的药代动力学特征，为制定多次耐受和药代动力学研究及II期临床试验给药方案提供依据。

开始日期2017-05-16

申办/合作机构

广东八加一医药有限公司

[+1]

100 项与 eNOS x EEF1A1 相关的临床结果

登录后查看更多信息

100 项与 eNOS x EEF1A1 相关的转化医学

登录后查看更多信息

0 项与 eNOS x EEF1A1 相关的专利（医药）

登录后查看更多信息

项与 eNOS x EEF1A1 相关的文献（医药）

2018-01-01·Circulation Journal3区 · 医学

Neuroprotection Mediated by Upregulation of Endothelial Nitric Oxide Synthase in Rho-Associated, Coiled-Coil-Containing Kinase 2 Deficient Mice

3区 · 医学

Article

作者: Soydan, Guray ; Sladojevic, Nikola ; Salomone, Salvatore ; Liao, James K. ; Tabit, Corey E. ; Noma, Kensuke ; Li, Yuxin ; Hiroi, Yukio ; Moskowitz, Michael A. ; Kim, Hyung-Hwan

BACKGROUNDRho-associated kinases (ROCK1 and ROCK2) are important regulators of the actin cytoskeleton and endothelial nitric oxide synthase (eNOS). Because the phosphorylation of eukaryotic elongation factor-1A1 (eEF1A1) by ROCK2 is critical for eNOS expression, we hypothesized that this molecular pathway may play a critical role in neuroprotection following focal cerebral ischemia.Methods and Results:Adult male wild-type (WT) and mutant ROCK2 and eNOS^-/-mice were subjected to middle cerebral artery occlusion (MCAO), and cerebral infarct size, neurological deficit and absolute cerebral blood flow were measured. In addition, aortic endothelium-dependent response to acetylcholine, N^G-nitro-L-arginine methyl ester (L-NAME) and sodium nitroprusside were assessed ex vivo. Endothelial cells from mouse brain or heart were used to measure eNOS and eEF1A activity, as well as NO production and eNOS mRNA half-life. In global hemizygous ROCK2^+/-and endothelial-specific EC-ROCK2^-/-mice, eNOS mRNA stability and eNOS expression were increased, which correlated with enhanced endothelium-dependent relaxation and neuroprotection following focal cerebral ischemia. Indeed, when ROCK2^+/-mice were place on an eNOS^-/-background, the neuroprotective effects observed in ROCK2^+/-mice were abolished.CONCLUSIONSThese findings indicate that the phosphorylation of eEF1A1 by ROCK2 is physiologically important for eNOS expression and NO-mediated neuroprotection, and suggest that targeting endothelial ROCK2 and eEF1A may have therapeutic benefits in ischemic stroke and cardiovascular disease.

2012-10-01·Stroke1区 · 医学

A Pentapeptide Monocyte Locomotion Inhibitory Factor Protects Brain Ischemia Injury by Targeting the eEF1A1/Endothelial Nitric Oxide Synthase Pathway

1区 · 医学

Article

作者: Zhang, Dazhi ; Yang, Pengyuan ; Xiong, Qinhui ; Li, Dong ; Zhang, Yuefan ; Wang, Xiao-Fan ; Li, Fan ; Lin, Yang ; Rui, Yao-Cheng ; Chen, Jun

Background and Purpose— Ischemic stroke is a major cause of death worldwide but lacks viable treatment or treatment targets. Monocyte locomotion inhibitory factor (MLIF) is a small heat-stable pentapeptide produced by Entamoeba histolytica in axenic culture, which is supposed to protect the brain from ischemic injury; the mechanism, however, remains unknown. In this study, we further investigated the mechanism underlying the protective role of MLIF in brain ischemia. Methods—A middle cerebral artery occlusion model in rats was used for detecting the effect of MLIF in the brain ischemia in vivo. To identify targets of MLIF in brain endothelial cells, we performed immunoprecipitation of biotin-conjugated MLIF and mass spectrometry.Results—MLIF can protect the brain from ischemic injury in vivo, yielding decreased ischemic volume, prolonged survival, and improved neurological outcome. In vitro studies showed that MLIF displayed protective effects through inhibition of expression of pathological inflammatory adhesion molecules and enhancing endothelial nitric oxide synthase expression and nitric oxide release in the cerebrovascular endothelium. The target screening experiments demonstrated binding of MLIF to the ribosomal protein translation elongation factor eEF1A1. MLIF enhanced endothelial nitric oxide synthase expression through stabilization of endothelial nitric oxide synthase mRNA, and eEF1A1 was shown to be necessary for this enhanced expression. Knockdown of eEF1A1 or inhibition of endothelial nitric oxide synthase attenuated MLIF-mediated inhibition of adhesion molecule expression.Conclusions—In this study, we identified a new potential pharmacologically targetable mechanism underlying MLIF's protective effects in brain ischemia through the eEF1A1/endothelial nitric oxide synthase pathway.

2008-09-12·Circulation Research1区 · 医学

Tumor Necrosis Factor-α Downregulates Endothelial Nitric Oxide Synthase mRNA Stability via Translation Elongation Factor 1-α 1

1区 · 医学

Article

作者: Sun, Jianxin ; You, Bei ; Liao, James K. ; Chen, Shao-Ping ; Yan, Guijun

Endothelium-derived nitric oxide (NO) is an important regulator of vascular function. NO is produced by endothelial NO synthase (eNOS), whose expression is downregulated by tumor necrosis factor (TNF)-α at the posttranscriptional level. To elucidate the molecular basis of TNF-α–mediated eNOS mRNA instability, eNOS 3′ untranslated region (3′-UTR) binding proteins were purified by RNA affinity chromatography from cytosolic fractions of TNF-α–stimulated human umbilical vein endothelial cells (HUVECs). The formation of 3′-UTR ribonucleoprotein complexes, with molecular weight of 52 and 57 kDa, was increased by TNF-α. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis of the 52-kDa protein identified 3 peptides that comprise the peptide sequence of translation elongation factor 1-α 1 (eEF1A1). In HUVECs, TNF-α rapidly increased eEF1A1 expression, which is maximal after 1 hour and persists for up to 48 hours. RNA gel mobility-shift and UV cross-linking assays indicated that recombinant glutathione S -transferase–eEF1A1 fusion protein specifically binds to a UC-rich sequence in the 3′-UTR of eNOS mRNA. In addition, the domain III of eEF1A1 mediates the binding of eNOS 3′-UTR in eEF1A1. Overexpression of eEF1A1 markedly attenuated the expression of eNOS and luciferase gene fused with eNOS 3′-UTR in both COS-7 cells and bovine aortic endothelial cells (BAECs). Furthermore, adenovirus-mediated overexpression of eEF1A1 increased eNOS mRNA instability, whereas knockdown of eEF1A1 substantially attenuated TNF-α–induced destabilization of eNOS mRNA and downregulation of eNOS expression in HUVECs. These results indicate that eEF1A1 is a novel eNOS 3′-UTR binding protein that plays a critical role in mediating TNF-α–induced decrease in eNOS mRNA stability.