Small molecule PIM kinase inhibitors as a novel class of oral anthelmintic drugs to treat whipworms and hookworms
About a quarter of the world's population is infected with soil-transmitted helminths (STH), which particularly impact communities lacking proper hygiene, sanitation, and clean water access. These infections, prevalent among children, can lead to various health issues and growth impairment. Currently, treatment options are limited, and drug resistance is emerging as a concern. Prior research identified metabolic 'chokepoint' enzymes shared across nematodes and identified small molecule inhibitors with broad anthelmintic activity. Among these, carnitine palmitoyl transferases (CPT1/CPT2) inhibitors showed promise against intestinal and filarial worms. Another target, 1-phosphotidylinositol-4-kinase (PI4K), was inhibited by Torin 1, effective against A. ceylanicum hookworms and T. muris whipworms. PIM kinases, known for promoting cell survival and growth, emerged as potential enzyme targets. RNA-seq analysis can be used to identify putative PIM kinase targets and downstream-affected pathways, relative to negative DMSO controls and positive control anthelmintics.