FNDR-20123 是一种有效、安全、首创的抗疟疾 HDAC 抑制剂，对疟原虫和人类 HDAC 的 IC50 分别为 31 nM 和 3 nM。FNDR-20123 对恶性疟原虫 (Plasmodium falciparum) 无性期 (IC50=41 nM) 和性血期 (雄性配子体 IC50=190 nM) 具有抗疟疾活性。FNDR-20123 抑制 HDAC1，HDAC2，HDAC3，HDAC6，HDAC8 的 IC50 分别为 25，29，2，11，282 nM，并在纳摩尔浓度下抑制 III 类
FNDR-20123 is a safe, first-in-class, and orally active anti-malarial HDAC inhibitor with IC50s of 31 nM and 3 nM for Plasmodium and human HDAC, respectively. FNDR-20123 exerts anti-malarial activity against Plasmodium falciparum asexual stage (IC50=41 nM) and sexual blood stage (IC50=190 nM for male gametocytes). FNDR-20123 inhibits HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8 (IC50=25/29/2/11/282 nM, respectively.) and inhibits Class III HDAC isoforms at nanomolar concentrations[1].
FNDR-20123 is active against all resistant strains tested so far, which will be highly valuable in eliminating the rapidly evolving drug-resistant parasite[1].
FNDR-20123 (10-50 mg/kg; p.o.; bw for 4 days) is also able to reduce parasitaemia significantly in a mouse model for P. falciparum infection[1].
[1]. Potluri V, et al. Discovery of FNDR-20123, a histone deacetylase inhibitor for the treatment of Plasmodium falciparum malaria. Malar J. 2020;19(1):365. Published 2020 Oct 12.
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