Held Jana, Jeyaraj Sankarganesh, Kreidenweiss Andrea
Institut für Tropenmedizin, Eberhard Karls Universität , Wilhelmstraße 27, D-72074 Tübingen , Germany +49 7071 29 85569 ; +49 7071 295189 ;
Expert Opin Investig Drugs. 2015 Mar;24(3):363-82. doi: 10.1517/13543784.2015.1000483. Epub 2015 Jan 7.
Malaria is a major health problem in endemic countries and chemotherapy remains the most important tool in combating it. Treatment options are limited and essentially rely on a single drug class - the artemisinins. Efforts are ongoing to restrict the evolving threat of artemisinin resistance but declining sensitivity has been reported. Fueled by the ambitious aim of malaria eradication, novel antimalarial compounds, with improved properties, are now in the progressive phase of drug development.
Herein, the authors describe antimalarial compounds currently in Phase II clinical development and present the results of these investigations.
Thanks to recent efforts, a number of promising antimalarial compounds are now in the pipeline. First safety data have been generated for all of these candidates, although their efficacy as antimalarials is still unclear for most of them. Of particular note are KAE609, KAF156 and DSM265, which are of chemical scaffolds new to malaria chemotherapy and would truly diversify antimalarial options. Apart from SAR97276, which also has a novel chemical scaffold that has had its development stopped, all other compounds in the pipeline belong to already known substance classes, which have been chemically modified. At this moment in time, there is not one standout compound that will revolutionize malaria treatment but several compounds that will add to its control in the future.
疟疾是流行国家的一个主要健康问题,化疗仍然是对抗疟疾最重要的工具。治疗选择有限,基本上依赖于单一药物类别——青蒿素。目前正在努力应对青蒿素耐药性不断演变的威胁,但已有青蒿素敏感性下降的报道。在消除疟疾这一宏伟目标的推动下,具有改进特性的新型抗疟化合物目前正处于药物开发的进展阶段。
在此,作者描述了目前处于II期临床开发阶段的抗疟化合物,并展示了这些研究的结果。
由于近期的努力,现在有一些有前景的抗疟化合物正在研发中。所有这些候选化合物都已产生了初步安全性数据,尽管它们作为抗疟药的疗效对其中大多数来说仍不明确。特别值得注意的是KAE609、KAF156和DSM265,它们具有疟疾化疗中全新的化学骨架,将真正使抗疟选择多样化。除了SAR97276(其也有一个已停止开发的新型化学骨架)之外,研发中的所有其他化合物都属于已知物质类别,只是进行了化学修饰。目前,没有一种突出的化合物会彻底改变疟疾治疗,但有几种化合物将在未来增强对疟疾的控制。