更新于：2024-11-01

PfeEF2

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 PfeEF2 相关的药物

Cabamiquine

靶点

PfeEF2

作用机制

PfeEF2抑制剂

在研机构

Merck Healthcare KGaA [+1]

原研机构

MMV Medicines for Malaria Venture [+1]

在研适应症

疟疾 [+2]

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 PfeEF2 相关的临床试验

NCT05974267 / Recruiting临床2期

Phase 2a Proof-of-Concept, Multicenter, Randomized, Open Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of a Single Dose of the Combination M5717-pyronaridine as Chemoprevention in Asymptomatic Adults and Adolescents With Plasmodium Falciparum Malaria Infection (CAPTURE-2)

This study will evaluate the efficacy and safety of a single dose of M5717 plus pyronaridine tetraphosphate in clearing current Plasmodium falciparum infection and protecting against recurrent infections in asymptomatic adults and adolescents. The study will also assess the duration of protection provided by different doses of M5717 plus pyronaridine and the additional contribution of M5717 to the duration of protection using external study data.

开始日期2023-11-28

申办/合作机构

Merck Healthcare KGaA

NCT05689047 / Active, not recruiting临床2期

Phase IIa Proof of Concept, Multicenter, Randomized, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of the Combination M5717 Plus Pyronaridine Administered Once Daily for 1 or 2 Days to Adults and Adolescents With Acute Uncomplicated Plasmodium Falciparum Malaria (CAPTURE 1)

The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetic of the combination M5717 plus pyronaridine in participants with acute uncomplicated Plasmodium falciparum malaria. Pyramax (Artesunate/Pyronaridine) will act as an internal control providing reference safety data and a benchmark for the efficacy evaluation.

开始日期2023-03-29

申办/合作机构

Merck Healthcare KGaA

NL-OMON49971 / CompletedN/A

A Phase Ib, Randomized, Double-Blind, Placebo Controlled, Sequential Study of Single Oral Doses of M5717 to Explore the Chemoprophylactic Activity of M5717 in a Controlled Plasmodium falciparum Sporozoite Challenge Model in Healthy Participants - Chemoprophylactic Activity of M5717 in PfSPZ Challenge Model

开始日期2020-09-08

申办/合作机构

Merck & Co., Inc.

100 项与 PfeEF2 相关的临床结果

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100 项与 PfeEF2 相关的转化医学

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0 项与 PfeEF2 相关的专利（医药）

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项与 PfeEF2 相关的文献（医药）

2024-12-01·Antonie van Leeuwenhoek

Expression of Staphylococcus aureus translation elongation factor P is regulated by a stress-inducible promotor

Article

作者: Zou, Long ; Xiang, Weiwei ; Long, Zhong-Er ; Zheng, Xingxing ; Sun, Xiuhui ; Ni, Haiyan

Translation elongation factor P, expressed by the efp gene, is a conserved protein closely related to bacterial virulence and environmental stress regulation responses, however, little is known about the efp gene expression regulations. Here, the strain of Staphylococcus aureus subsp. aureus NCTC 8325 was taken as the research object and cultured under different conditions, including different culture temperatures, pH, and antibiotics, to study the expression of the efp gene in S. aureus by qRT-PCR, the results showed that the expression of the efp gene is upregulated under high temperature (40 °C), acidic (pH 5.4) or alkaline (pH 9.4) culture conditions, but upregulated early and downregulated later under the conditions of 0.5 MIC antibiotics (chloramphenicol at the final concentration of 2 μg/mL and vancomycin at the final concentration of 0.25 μg/mL), indicating that the efp promoter in S. aureus is inducible. The efp promoter sequence and structure in S. aureus were predicted by bioinformatics methods, and the predicted promoter was validated by constructing a promoter-probe vector and a series of promoter mutants, the results showed that the efp promoter sequence in S. aureus, named Pro, located in 1,548,179-1,548,250 of the S. aureus genome (NC_007795.1), and the sequence of - 10 element is CCTTATAGT, - 35 element is TTTACT. The results above could lay a foundation for screening transcription factors involved in the expression of the efp gene and then exploring the transcriptional regulation mechanism of EF-P in S. aureus.

2024-05-01·Cell Reports

Decrypting the functional design of unmodified translation elongation factor P

Article

作者: Krafczyk, Ralph ; Tomasiunaite, Urte ; Jung, Kirsten ; Imhof, Axel ; Kielkowski, Pavel ; Forné, Ignasi

Bacteria overcome ribosome stalling by employing translation elongation factor P (EF-P), which requires post-translational modification (PTM) for its full activity. However, EF-Ps of the PGKGP subfamily are unmodified. The mechanism behind the ability to avoid PTM while retaining active EF-P requires further examination. Here, we investigate the design principles governing the functionality of unmodified EF-Ps in Escherichia coli. We screen for naturally unmodified EF-Ps with activity in E. coli and discover that the EF-P from Rhodomicrobium vannielii rescues growth defects of a mutant lacking the modification enzyme EF-P-(R)-β-lysine ligase. We identify amino acids in unmodified EF-P that modulate its activity. Ultimately, we find that substitution of these amino acids in other marginally active EF-Ps of the PGKGP subfamily leads to fully functional variants in E. coli. These results provide strategies to improve heterologous expression of proteins with polyproline motifs in E. coli and give insights into cellular adaptations to optimize protein synthesis.

2023-07-01·Open forum infectious diseases

Differential Effects of Antimalarial Drugs on Parasite Clearance Rates Are Reflected by Plasmodium falciparum Ring Ratio.

Article

作者: Musaya, Janelisa ; Seydel, Karl ; Zhang, Bo ; Kawaza, Kondwani ; Saidi, Alexuse M ; Taylor, Terrie ; Jiang, Melody

BackgroundThe location of Plasmodium falciparum within the body is determined by the life cycle of the parasite; young rings are in the peripheral blood, whereas mature parasites are sequestered in deep tissues. We can calculate a "ring ratio," the proportion of parasites in the periphery to the total number of parasites in the body. Artesunate acts on all parasite life stages, whereas quinine is effective only on sequestered parasites. Children with cerebral malaria (CM) treated with artesunate clear parasites faster than those treated with quinine. In this study, we established the relationship between ring ratio and parasite clearance rate and used the ring ratio to determine if the benefit derived from artesunate treatment could be attributed to its broader effect on life cycle stages.MethodsRing ratios were calculated for 400 hospitalized children with CM in Blantyre, Malawi between 2010 and 2019 (quinine: 2010-2013, artesunate: 2014-2019).ResultsIn both treatment groups, parasite clearance rates were positively associated with the ring ratios, with a stronger association in the artesunate era than the quinine era. In the quinine era, an increase of 1-unit log₁₀ difference between parasitemia and plasma P falciparum histidine-rich protein 2 (a proxy for ring ratio) resulted in a 0.27-unit increase in the parasite clearance rate, whereas in the artesunate era an equal increase resulted in a 0.41-unit increase (P = .04 for the difference).ConclusionsThis analysis provides in vivo evidence supporting the hypothesis that more rapid parasite clearance rates in artesunate recipients are due to its superiority over quinine in killing ring-stage parasites.