更新于：2024-11-01

EPT

更新于：2024-11-01

基本信息

别名

Enoylpyruvate transferase、EPT、murZ

+ [2]

简介

Cell wall formation (PubMed:1512209). Adds enolpyruvyl to UDP-N-acetylglucosamine (PubMed:1512209, PubMed:20392080). Target for the antibiotic fosfomycin.

关联

项与 EPT 相关的药物

Fosfomycin Tromethamine

磷霉素氨丁三醇

靶点

EPT

作用机制

EPT抑制剂

在研机构

Zambon GmbH [+3]

原研机构

Zambon GmbH

在研适应症

泌尿道感染

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区-

首次获批日期1988-01-01

项与 EPT 相关的临床试验

CTR20242961 / CompletedN/A

江苏联环药业股份有限公司研制的磷霉素氨丁三醇颗粒（3 g）与Zambon Switzerland Ltd.生产的磷霉素氨丁三醇颗粒（3 g）在中国健康受试者中进行的随机、开放、单剂量、两序列、两周期、交叉、空腹状态下的生物等效性研究

以江苏联环药业股份有限公司研制的磷霉素氨丁三醇颗粒（规格：3 g）为受试制剂，以Zambon Switzerland Ltd.生产的磷霉素氨丁三醇颗粒（商品名：Monurol®，规格：3 g）为参比制剂，考察两制剂在空腹状态下单次给药的药代动力学参数及相对生物利用度，评价两制剂是否具有生物等效性；同时评价两种制剂在健康人体中的安全性和耐受性。

开始日期2024-08-21

申办/合作机构

江苏联环药业股份有限公司

NCT06017479 / Completed临床1/2期

Effectiveness of Single Dose Fosfomycin and Single Dose Levofloxacin as Pre-urodynamic Antibiotic Prophylaxis for Urinary Tract Infection Prevention in Post-Urodynamic Examination

The goal of this clinical trial is to compare the use of single dose fosfomycin and single dose levofloxacin as pre-urodynamic antibiotic prophylaxis for urinary tract infection prevention post-urodynamic in patients with lower urinary tract symptoms. The main question[s] it aims to answer are:
* What is the difference between the effectiveness of administering a single dose of fosfomycin and levofloxacin prior to the procedure in terms of the incidence rate of urinary tract infection (UTI) post-urodynamic examination?
* What is the incidence rate of UTI in the administration of single-dose fosfomycin and levofloxacin prior to the procedure on the incidence rate of UTI post-urodynamic examination? Participants fulfilling the inclusion criteria will be taken their history and vital signs and consume either fosfomycin or levofloxacin based on the randomisation prior to urodynamic procedure. Afterwards, participants will undergo urine analysis 4 days post urodynamic to evaluate if there's any urinary tract infection. If there is any bacteria present, the sample will be cultured to identify bacteria found in the urine.

开始日期2022-12-30

申办/合作机构

University of Indonesia

CTRI/2022/08/045068 / Recruiting临床3期

A Multicentric, Randomized, Open Label, Controlled, Phase III Clinical Trial to evaluate theEfficacy, Safety and Tolerability of Fosfomycin (Trometamol) Powder 3 g versusCiprofloxacin Tablets 750 mg in patients with Chronic Bacterial Prostatitis and Chronic Pelvic Pain Syndrome

开始日期2022-09-01

申办/合作机构

SRS Pharmaceuticals Pvt Ltd.

100 项与 EPT 相关的临床结果

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100 项与 EPT 相关的转化医学

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0 项与 EPT 相关的专利（医药）

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152

项与 EPT 相关的文献（医药）

2024-12-01·Applied Microbiology and Biotechnology

The identification of a key gene highlights macrocyclic ring’s role in trichothecene toxicity

Article

作者: Martínez-Reyes, Natalia ; McCormick, Susan P ; Cardoza, Rosa E ; Vermillion, Karl ; Gutiérrez, Santiago ; Rodríguez-González, Álvaro ; Cardoza, Rosa E. ; Casquero, Pedro A ; McCormick, Susan P. ; Busman, Mark ; Proctor, Robert H. ; Casquero, Pedro A. ; Proctor, Robert H

Trichothecenes are toxins produced by certain species from several fungal genera, including Aspergillus, Fusarium, Isaria, Paramyrothecium, Stachybotrys, Trichoderma, and Trichothecium. These toxins are of interest because they contribute to the toxigenicity, plant pathogenicity, and/or biological control activities of some fungi. All trichothecenes have the same core (12,13-epoxytrichothec-9-ene or EPT) structure but can differ from one another by the presence or absence of a macrocyclic ring formed from polyketide and isoprenoid substituents esterified to carbon atoms 4 and 15 of EPT, respectively. Genes required for formation and some modifications of EPT have been elucidated, but almost nothing is known about genes specific to the formation of the macrocyclic ring. Therefore, we used genomic, transcriptomic, metabolomic, and gene deletion analyses to identify genes that are required specifically for the formation of the macrocyclic ring. These analyses identified one gene, TRI24, that is predicted to encode an acyltransferase and that is required for macrocyclic ring formation during biosynthesis of macrocyclic trichothecenes by the fungus Paramyrothecium roridum. In addition, a TRI24 deletion mutant of P. roridum caused less severe disease symptoms on common bean and had less antifungal activity than its wild-type progenitor strain. We propose that the reduced aggressiveness and antifungal activity of the mutant resulted from its inability to produce trichothecenes with a macrocyclic ring. To our knowledge, this is the first report of a gene required specifically for the formation of the macrocyclic ring of trichothecenes and that loss of the macrocyclic ring of trichothecenes can alter the biological activities of a fungus. KEY POINTS: • TRI24 gene is found in all known macrocyclic trichothecene-producing fungi. • A tri24-deletion mutant exhibits a reduction in antifungal and plant disease activities. • TRI24 is the first described gene specific to macrocyclic trichothecene biosynthesis.

2024-12-01·Applied Microbiology and Biotechnology

Analysis of substrate specificity of cytochrome P450 monooxygenases involved in trichothecene toxin biosynthesis

Article

作者: Martínez-Reyes, Natalia ; Rodríguez-Fernández, Joaquín ; McCormick, Susan P ; Busman, Mark ; Proctor, Robert H ; Cardoza, Rosa E ; Gutiérrez, Santiago

AbstractTrichothecenes are a structurally diverse family of toxic secondary metabolites produced by certain species of multiple fungal genera. All trichothecene analogs share a core 12,13-epoxytrichothec-9-ene (EPT) structure but differ in presence, absence and types of substituents attached to various positions of EPT. Formation of some of the structural diversity begins early in the biosynthetic pathway such that some producing species have few trichothecene biosynthetic intermediates in common. Cytochrome P450 monooxygenases (P450s) play critical roles in formation of trichothecene structural diversity. Within some species, relaxed substrate specificities of P450s allow individual orthologs of the enzymes to modify multiple trichothecene biosynthetic intermediates. It is not clear, however, whether the relaxed specificity extends to biosynthetic intermediates that are not produced by the species in which the orthologs originate. To address this knowledge gap, we used a mutant complementation-heterologous expression analysis to assess whether orthologs of three trichothecene biosynthetic P450s (TRI11, TRI13 and TRI22) from Fusarium sporotrichioides, Trichoderma arundinaceum, and Paramyrothecium roridum can modify trichothecene biosynthetic intermediates that they do not encounter in the organism in which they originated. The results indicate that TRI13 and TRI22 could not modify the intermediates that they do not normally encounter, whereas TRI11 could modify an intermediate that it does not normally encounter. These findings indicate that substrate promiscuity varies among trichothecene biosynthetic P450s. One structural feature that likely impacts the ability of the P450s to use biosynthetic intermediates as substrates is the presence and absence of an oxygen atom attached to carbon atom 3 of EPT.

2024-10-01·Science of The Total Environment

Bioindicator aquatic insects at risk from climate change in a biodiversity hotspot

Article

作者: Tourinho, Luara ; Farjalla, Vinicius F ; Souza, Natália F ; Rocha, Diogo S B ; Leal, Juliana S ; Vale, Mariana M

Climate change can affect biological assemblages by shifting their species' geographic range and changing species richness. Aquatic insects represent more than half of the freshwater animal species but have been neglected mainly in climate change assessments, particularly in tropical ecosystems. Among the aquatic insect taxa, Ephemeroptera, Plecoptera, and Trichoptera (EPT) are well-known bioindicators of environmental changes and encompass an essential metric for rivers and streams' biomonitoring. Here, we use ecological niche models to project the impact of climate change on the distribution range and richness of EPT in the Atlantic Forest biodiversity hotspot. We found EPT to be at high risk from future climate change, with Plecoptera as the order of greatest concern. We projected range contraction of ca. 90 % of the analyzed EPT genera, resulting in a reduction in the richness of EPT genera under future climatic conditions. We projected >50 % contraction in the distribution of 50 % of Plecoptera, ≈14 % of Trichoptera, and ≈7 % of Ephemeroptera genera. The remaining climatically suitable regions in the Atlantic Forest are concentrated in the high-altitude areas, which may act as climate refuges for EPT biodiversity in the future. The projected changes in EPT's distribution range and richness may impact biomonitoring programs conducted in tropical ecosystems. Restricting EPT's geographic distribution may undermine its potential as a bioindicator and influence the composition of EPT assemblages at reference sites, which may lead to shifting baseline conditions. We reinforce the importance of considering future climatic conditions when planning long-term biomonitoring and priority areas for conservation.

项与 EPT 相关的新闻（医药）

2023-12-29

·CPHI制药在线

浅析药物设计学之前药

关注并星标CPHI制药在线导读：在市场上取得成功的药物的传统途径始于识别疾病和适当的药物靶点，找到先导化合物和药效团，并优化药物先导分子与靶标的相互作用。由于分子的药代动力学（PK）较差，药物开发计划仍可能失败。PK 的缺点可能与四个构成障碍中的每一个有关，即吸收、分布、代谢和排泄（称为 ADME）。在许多成功上市的药物案例中，药理学先导化合物得到了显著优化，以改善其药代动力学，并使用前药克服这些障碍。根据定义，前药是治疗活性分子的衍生物或前体，它们通过自发过程（例如水解降解）或通过生物催化机制在体内发生生物转化成其活性形式。前药策略在药物递送中的应用通常旨在帮助药物克服物理或隐喻障碍，以增强药物的可递送有效载荷。这些障碍包括（但不限于）水溶性差-这会显着限制药物在药用中的效用；从胃肠道吸收到血液中不良；细胞进入率低等。在2015年进入美国市场的小分子（非生物）药物中，32个分子中有7个是前药。前药的一个突出例子是索非布韦，是2015年第二畅销的药物。正文：前药生物转化过程可任意分为两类，1）前药降解与药物回收，2）前药活化。对于前药降解类，前药分子代表母体药物的偶联物；生物转化反应包括去除掩蔽基团（通常称为“促性”）；分子的化学复杂性降低。在前药活化类别（也称为“生物前体”类别）中，前药经历了化学修饰（例如氨基甲胺到羰基转化），其中化学复杂性相对不变，而治疗活性显着增强。前药的设计策略首先取决于母体药物分子的结构特征，特别是化学官能团的可用性，这些官能团可用于通过修饰基团的附着等来掩盖药物的药效学活性。第二个同样重要的因素是与药物释放的生物转化机制有关。这个过程可能是自发的，但在总体上，药物变化（通过回收或活化）是通过酶促过程进行的。药物化学中的常规前药通常旨在实现药物的定量回收，这是主要目标。在这些应用中，通常很少或根本不考虑药物在体内的分布，并且执行生物转化的酶可以分布在整个体内（例如酯酶、磷酸酯酶）。在某些情况下，特异性酶可能主要在特定器官内表达，例如在肝脏中。酶前药疗法（EPT）属于一种比较特别的前药亚类，其生物转化由体内特定位置的酶执行，通过这种方式，药物的恢复或活化仅在酶的位置实现。与一般药物前药相比，在EPT的情况下，定量药物回收不那么重要，主要目标是实现特定部位的药物回收。酶在所需位点的定位可以通过多种方式完成。从历史上看，抗体定向酶前药治疗（antibody-directed enzyme-prodrug therapy， ADEPT）是EPT最早获得成功的案例。ADEPT的例子通常依赖于通过药物回收机制进行的细胞外前药生物转化。目前正在进行的临床试验数量最多的EPT模式是基因定向EPT（gene-directed EPT，GDEPT），在这种情况下，前药转化酶在前药转化时由细胞表达。辛伐他汀（图1）是市场上最古老、最知名的前药之一。其作用机制涉及其六元内酯环的体内水解，最后产生与 HMG-CoA（羟甲基戊二酰辅酶 A）结构相似的活性代谢物。辛伐他汀的水解代谢产物与HMG-CoA竞争HMG-CoA还原酶，催化HMG-CoA转化为甲羟戊酸，从而限制胆固醇生物合成。图1辛伐他汀结构式（图片来自网络）腺苷二磷酸受体阻滞剂，尤其是噻吩并吡啶类药物，已被证明是优良的血小板聚集抑制剂，是预防凝血障碍的首选药物。这类药物的血小板抑制机制主要是通过阻断血小板的P2Y12受体来实现的。研究报道氯吡格雷（图2）抑制胶原和凝血酶诱导的血小板聚集。最近关于氯吡格雷和普拉格雷的大多数临床试验是为了进一步确定药物的最佳剂量、其方案以及它们与其它常见慢性病（如糖尿病）的相互作用。因此，预计最近的这些临床试验将有助于制定针对急性冠脉综合征、心绞痛、心力衰竭、心房颤动等疾病的未来指南。图1辛伐他汀结构式（图片来自网络） ANAVEX 2-73是一种小分子孤儿药，由 Anavex Life Sciences Corp. 开发，可激活神经元中的 sigma-1受体。这种激活通过预防或减少蛋白质错误折叠、细胞应激、线粒体功能障碍和氧化应激来调节与神经退行性变相关的过程。ANAVEX 2-73 是一种氨基四氢呋喃，通过其叔胺基团的去甲基化而被活化。前药设计的其它原理还有：1.将羧基成酯；2.NO供体型药物，主要是以已知药物或活性化合物的结构为母核，与NO 供体通过各种连接基团结合而成的前药，它可在体内经相关酶或非酶作用释放原药和NO；3.多步转化类型前药，卡培他滨(capecitabine)是5-氟尿嘧啶的三级前体药物，口服后经过3步活化于肿瘤组织中释放出原药。首先在肝脏中经过羧酸酯酶水解，其次位于肝脏和肿瘤组织中的胞嘧啶核苷(胞苷)脱氨酶氨解，最后在肿瘤细胞内胸腺嘧啶核苷磷酸酶代谢成5-FU ，其结构通过肿瘤相关性血管因子胸苷磷酸化酶在肿瘤所在部位才转化而成，从而最大程度的降低了5-氟尿嘧啶对正常人体细胞的损害，避免了一系列的不良反应，因而可以作为长期服用的抗肿瘤药物。文献详情： 1.Walther R，Rautio J，Zelikin A N. Prodrugs in medicinal chemistry and enzyme prodrug therapies[J]. Advanced drug delivery reviews，2017，118: 65-77. 2.Najjar A，Najjar A，Karaman R. Newly developed prodrugs and prodrugs in development; an insight of the recent years[J]. Molecules，2020，25(4): 884. 作者简介：roger，广东广州人，硕士研究生，工程师，主要研究方向为分析方法学，仪器原理与研制，凝聚态物理，电学理论与超导体理论，理论物理等等。2023金笔奖火热投票中快来选出您喜爱的原创文章！来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

抗体药物偶联物核酸药物医药出海