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蛋白酶体作为一种药物靶点在原生动物疾病中的应用

Proteasome as a Drug Target in Trypanosomatid Diseases.

机构信息

Laboratório de Síntese de Moléculas Medicinais (LaSMMed), Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Londrina, Londrina, Brazil.

出版信息

Curr Drug Targets. 2023;24(10):781-789. doi: 10.2174/1389450124666230719104147.

Abstract

Some diseases caused by trypanosomatid parasites, like Leishmaniasis, Chagas Disease, and Human African Trypanosomiasis (HTA), are challenging to manage, mainly concerning pharmacological therapy because they are associated with vulnerable populations. Unfortunately, there is a lack of significant investments in the search for new drugs. Therefore, one of the strategies to aid the discovery of new drugs is to identify and inhibit molecular targets essential to the parasite's survival, such as the proteasome, which degrades most proteins in the parasite cells. Our study has presented several proteasome inhibitors with various pharmacophoric cores, and two of them, 5, and 13, have stood out in the clinical phase of treatment for leishmaniasis.

摘要

一些由原生动物寄生虫引起的疾病,如利什曼病、恰加斯病和人类非洲锥虫病(HTA),难以治疗,主要是因为药物治疗方面存在挑战,因为这些疾病与弱势群体有关。不幸的是,在寻找新药方面的投资非常有限。因此,发现新药的策略之一是识别和抑制对寄生虫生存至关重要的分子靶标,如蛋白酶体,它降解寄生虫细胞中的大多数蛋白质。我们的研究已经提出了几种具有不同药效团核心的蛋白酶体抑制剂,其中两种,即 5 和 13,在治疗利什曼病的临床阶段表现突出。

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