Hemozoin and antimalarial drug discovery.
Hemozoin and antimalarial drug discovery.
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DOI：
10.4155/fmc.13.113
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发表时间：
2013-08
影响因子：
4.2
通讯作者：
Wright DW
中科院分区：
文献类型：
--
作者：
Fong KY;Wright DW
最近，为了彻底根除疟疾，发起了开发更有效和负担得起的药物、控制蚊子和开发预防性疫苗的倡议。为此，诺华公司（英国萨里）和葛兰素史克公司（英国米德尔塞克斯）筛选了他们的大约200万个小分子的化学库，以获得抗疟疾特性，这导致了一组超过20，000个“高度可药物化”的初始命中。学术界的努力集中在特定的路径目标上。一个这样的高通量筛选工作一直集中在疟原虫色素形成，一个独特的血红素解毒途径中发现的疟疾寄生虫。本文综述了目前高通量筛选疟原虫色素抑制剂的方法及其局限性。在未来，必须开发新的方法来验证这些命中化合物在寄生虫中的作用机制。
Recent initiatives to develop more effective and affordable drugs, controlling mosquitoes and development of a preventative vaccine have been launched with the goal of completely eradicating malaria. To this end, Novartis (Surrey, UK) and GlaxoSmithKline (Middlesex, UK) screened their chemical libraries of approximately two million small molecules for antimalarial properties, which resulted in a set of over 20,000 ‘highly druggable’ initial hits. Efforts in academia are centered on specific pathway targets. One such high-throughput screening effort has been focused on hemozoin formation, a unique heme detoxification pathway found in the malaria parasite. This review discusses the current approaches and limitations of high-throughput screening discovery of hemozoin inhibitors. In the future, new methods must be developed to validate the mechanism of action of these hit compounds within the parasite.