FNDR-20123 free base, a pioneering and orally administered anti-malarial agent, acts as a Histone Deacetylase (HDAC) inhibitor, displaying potent efficacy with IC50 values of 31 nM for Plasmodium and 3 nM for human HDAC, respectively. It effectively targets both the asexual (IC50=41 nM) and sexual blood stages (IC50=190 nM for male gametocytes) of Plasmodium falciparum. Additionally, FNDR-20123 free base inhibits multiple HDAC isoforms, namely HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8, with respective IC50 values of 25, 29, 2, 11, and 282 nM, and displays nanomolar inhibitory concentrations against Class III HDAC isoforms [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]. Animal Model: P. falciparum Pf3D 70087/N9 in NODscidIL2Rγ null 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.