| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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]. | Animal Model: | P. falciparum Pf3D70087/N9 in NODscidIL2Rγnull mice (engrafted with human erythrocytes)[1] | | Dosage: | 10 and 50 mg/kg | | Administration: | P.o.; bw for 4 days | | Result: | Resulted in a significant reduction in parasitaemia with 6.5% and 2.57% parasitaemia at 10 and 50 mg/kg, respectively.
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| [IC 50]
human HDAC: 3 nM (IC50); Plasmodium HDAC: 31 nM (IC50); HDAC1: 25 nM (IC50); HDAC2: 29 nM (IC50); HDAC3: 2 nM (IC50); HDAC6: 11 nM (IC50); HDAC8: 282 nM (IC50); Plasmodium | [References]
[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. DOI:10.1186/s12936-020-03421-3 |
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