ACT-451840 是一种具有口服活性，强效低毒化合物，对敏感和耐药的恶性疟原虫株具有活性。ACT-451840 对 parasite 的所有无性血液阶段，起效快速。ACT-451840 的作用方式与青蒿素衍生物类似，具有非常迅速消除 parasite 的作用。ACT-451840 可以用于研究疟疾 。
ACT-451840 is an orally active, potent and low-toxicity compound, showing activity against sensitive and resistant plasmodium falciparum strains. ACT-451840 targets all asexual blood stages of the parasite, has a rapid onset of action. ACT-451840 behaves in a way similar to artemisinin derivatives, with very rapid onset of action and elimination of parasite. ACT-451840 can be used for the research of malarial[1][2][3].
ACT-451840 shows a 50 % inhibition concentration of 0.4 nM against the drug-sensitive P. falciparum NF54 strain. The IC50 value of ACT-451840 against the murine malaria parasite P. berghei is 13.5 nM in in vitro ex vivo assays.
ACT-451840 (10 and 60 mg kg) starts to show significant antimalarial effects (parasite reduction) in vivo at 20 mg/kg. ACT-451840 exhibits curative activity at 300 mg/kg and significant antimalarial effects already at 100 mg/kg. ACT-451840 shows excellent reduction at 30 mg/kg, resulting in 99.80 % activity[2]. ACT-451840 shows efficacy in the Plasmodium berghei mouse model[2].
[1]. Bruderer S, et al. First-in-humans study of the safety, tolerability, and pharmacokinetics of ACT-451840, a new chemical entity with antimalarial activity. Antimicrob Agents Chemother. 2015;59(2):935-942.
[2]. Boss C, et al. Discovery and Characterization of ACT-451840: an Antimalarial Drug with a Novel Mechanism of Action. ChemMedChem. 2016;11(18):1995-2014.
[3]. Le Bihan A, et al. Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling. PLoS Med. 2016;13(10):e1002138. Published 2016 Oct 4.
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