Drug target identification in protozoan parasites

被引:40
|
作者
Mueller, Joachim [1 ]
Hemphill, Andrew [1 ]
机构
[1] Univ Bern, Inst Parasitol, Vetsuisse Fac, Langgass Str 122, CH-3012 Bern, Switzerland
基金
瑞士国家科学基金会; 美国国家卫生研究院;
关键词
Apicomplexa; drug design; kinetoplastida; mode of action; repurposing; target; PROTEIN-KINASE; 1; TOXOPLASMA-GONDII; IN-VITRO; PLASMODIUM-FALCIPARUM; GIARDIA-LAMBLIA; N-MYRISTOYLTRANSFERASE; DIHYDROOROTATE DEHYDROGENASE; PHOSPHODIESTERASE INHIBITORS; AFRICAN TRYPANOSOMIASIS; ARTEMISININ DERIVATIVES;
D O I
10.1080/17460441.2016.1195945
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications.Areas covered: Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail.Expert opinion: Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses.
引用
收藏
页码:815 / 824
页数:10
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