Recent updates in the discovery and development of novel antimalarial drug candidates,RSC Medicinal Chemistry

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Recent updates in the discovery and development of novel antimalarial drug candidates
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2018-02-02 00:00:00 , DOI: 10.1039/c7md00637c
John Okombo ₁ , Kelly Chibale _{1,

2}

Affiliation

Though morbidity and mortality due to malaria have declined in the last 15 years, emerging resistance to first-line artemisinin-based antimalarials, absence of efficacious vaccines and limited chemotherapeutic alternatives imperil the consolidation of these gains. As a blueprint to steer future designs of new medicines, malaria drug discovery recently adopted a descriptive proposal for the ideal candidate molecules and drugs likely to successfully progress into the final stages of clinical development. As an audit of recent developments in the chemotherapy of malaria in the last five years, this review captures a landscape of diverse molecules at various stages of drug development and discusses their progress. In brief, we also discuss how omics data on Plasmodium has been extensively leveraged to identify potential vaccine candidates and putative targets of molecules in development and clinical use as well as map loci implicit in their modes of resistance. Future perspective on malaria drug development should involve a reconciliation of some of the challenges of the target candidate profiles (TCPs), specifically TCP3, with the promise of effective anti-hypnozoite medicines. Similarly, with the recent development of a humanized mouse model that can evaluate the prophylactic potential of candidate drugs, we argue for increased effort at identifying more liver-stage molecules, which are often only secondarily prioritized in conventional screening programs.

中文翻译：

新型抗疟候选药物发现和开发的最新进展

尽管疟疾引起的发病率和死亡率在过去 15 年中有所下降，但一线青蒿素抗疟药出现的耐药性、有效疫苗的缺乏以及化疗替代品有限，都危及了这些成果的巩固。作为指导未来新药设计的蓝图，疟疾药物发现最近通过了一项关于理想候选分子和药物的描述性提案，可能会成功进入临床开发的最后阶段。作为对过去五年疟疾化疗最新进展的回顾，这篇综述捕捉了药物开发各个阶段的不同分子的情况，并讨论了它们的进展。简而言之，我们还讨论了如何广泛利用疟原虫的组学数据来识别潜在的候选疫苗和开发和临床使用中分子的推定靶标，以及隐含在其耐药模式中的基因座图谱。疟疾药物开发的未来前景应涉及解决目标候选谱（TCP）（特别是 TCP3）的一些挑战，并有望提供有效的抗催眠药物。同样，随着最近开发出一种可以评估候选药物预防潜力的人源化小鼠模型，我们主张加大力度鉴定更多肝脏阶段分子，这些分子在传统筛选计划中通常只是次要优先考虑的。

更新日期：2018-02-02

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