This is the first report detailing complete PM4 gene analysis from Indian P. vivax isolates. Blast results of sequences of P. vivax plasmepsin 4 (PvPM4) shows 100% homology among isolates of P. vivax collected from different geographical regions of India.
We attached 2-aminoethylamino groups to allophenylnorstatine-containing plasmepsin (Plm) inhibitors and investigated SAR of the methyl or ethyl substitutions on the amino groups. Unexpectedly, compounds 22 (KNI-10743) and 25 (KNI-10742) exhibited extremely potent Plm II inhibitory activities (Ki <0.1 nM).
In vitro studies identified a plasmepsin inhibitor that could aid in the development of new treatments for malaria. Further details on the research, next steps and licensing status are discussed in the article.