"目录号: HY-14430
Anti-infection-
NITD609 是一种有效的抗疟疾药，对恶性疟原虫的IC50值约为 1 nM。
Parasite
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生物活性
Description
NITD609 is an potent antimalarial compound, withIC50of appr 1 nM againstP. falciparum.
IC50& Target
IC50: 1 nM (P. falciparum)[3]
In Vitro
NITD609 inhibitsT. gondiiwith a MIC90for tachyzoites of 5 μM and a MIC50of 1 μM, without toxicity to human foreskin fibroblasts (HFFs) at the highest concentration tested (10 μM)[1]. NITD609 is the most effective inhibitor of early gametocyte development at 50 and 500 nM. NITD609 shows a dose-dependent inhibiting effect on late gametocyte development[2]. NITD609 shows potent activities against a panel of culture-adaptedP. falciparumstrains, with ICIC50values of 0.5-1.4 nM. NITD609 is effective as artesunate with potency in the low nanomolar range (ICIC50values consistently <10 nM) against allP. falciparumandP. vivax isolates[3].
In Vivo
NITD609 shows favorable pharmacokinetic properties and displays single dose cure efficacy in a malaria mouse model. NITD609 (100 mg/kg) completely clearsP. bergheiinfection in all treated mice, and partial cure (50%) is achieved with a single oral dose at 30 mg/kg[3].
References
[1].Zhou Y, et al. Spiroindolone that inhibits PfATPase4 is a potent, cidal inhibitor of Toxoplasma gondii tachyzoites in vitro and in vivo. Antimicrob Agents Chemother. 2014;58(3):1789-92.
[2].van Pelt-Koops JC, et al. The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to anopheles mosquito vector. Antimicrob Agents Chemother. 2012 Jul;56(7):3544-8.
[3].Rottmann M, et al. Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010 Sep 3;329(5996):1175-80.