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Deorphanization of Schistosome Cytochrome P450

血吸虫细胞色素 P450 的脱孤儿化

基本信息

批准号：
9241969
负责人：
DAVID LEE WILLIAMS
金额：
$ 19.38万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-15 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9241969
关键词：
Adult Animals Antifungal Agents Arachidonic Acids Azoles Catabolism Cell membrane Cells Cessation of life Cholesterol Chronic Disease Clinical Communication Complement Critiques Cytochrome P450 Data Detoxification Process Development Disease Drug Metabolic Detoxication Drug Targeting Drug resistance Ecdysteroids Eicosanoids Enzymes Ergosterol Escherichia coli Family Foundations Fungal Components Genes Genome Goals Hormones Human Imidazole Infection Insecta Investigation Label Link Lipids Messenger RNA Metabolic Pathway Miconazole Molecular Target Orphan Oxides Parasites Pathway interactions Pharmaceutical Preparations Pharmacology Pharmacotherapy Poison Polyunsaturated Fatty Acids Praziquantel Praziquantel resistance Production Proteins RNA Interference Recombinant Proteins Recombinants Reproduction Research Proposals Retinoids Schistosoma Schistosoma mansoni Schistosomiasis Secosteroids Signal Pathway Signaling Molecule Structure-Activity Relationship Testing Vitamin A Vitamin D Xenobiotics Yeasts analog chemotherapy design disability drug development evidence base improved inhibitor/antagonist metabolomics neglect novel therapeutics protein function public health relevance scaffold screening steroid hormone

项目摘要

DESCRIPTION (provided by applicant): The goal of this R21 Exploratory/Developmental Research proposal is to identify the function of the only cytochrome P450 protein present in Schistosoma mansoni, a causative agent of schistosomiasis. We hypothesize that the unique schistosome cytochrome P450 is essential for worm communication, survival, reproduction, and development and that its function can be identified by linking it to specific metabolic pathways. We believe that understanding the function of this protein will identify critical signaling pathway and will be useful in the discovery of new drugs for schistosomiasis, an important, neglected disease with more than 200 million people infected resulting in 200,000 deaths annually and untold chronic illness and disability. Only one drug is available for schistosomiasis treatment and there are concerns that drug resistance is evolving.

描述(由申请人提供)：这项R21探索性/发展研究提案的目标是确定曼氏血吸虫中唯一存在的细胞色素P450蛋白的功能，曼氏血吸虫是血吸虫病的病原体。我们推测，独特的血吸虫细胞色素P450对虫子的交流、生存、繁殖和发育是必不可少的，其功能可以通过将其与特定的代谢途径联系起来来确定。我们相信，了解该蛋白的功能将识别关键的信号通路，并将有助于发现治疗血吸虫病的新药。血吸虫病是一种重要的、被忽视的疾病，每年有超过2亿人感染，导致20万人死亡，以及数不清的慢性疾病和残疾。目前只有一种药物可用于治疗血吸虫病，人们担心抗药性正在演变。