Plasmodium vivax phosphatidylinositol 4-kinase beta (PvPI4K beta)

Plasmodium vivax phosphatidylinositol 4-kinase beta (PvPI4K beta) is an essential lipid kinase that plays a critical role in the life cycle of the malaria parasite (McNamara et al., 2013). It is responsible for phosphorylating phosphatidylinositol to produce phosphatidylinositol 4-phosphate (PI4P), a key signaling molecule required for membrane trafficking, vesicular transport, and cytokinesis during parasite development (McNamara et al., 2013; Zeeman et al., 2016). PvPI4K beta is expressed across multiple stages of the Plasmodium life cycle, including the liver and asexual blood stages, making it a highly attractive target for both prophylaxis and treatment (Zeeman et al., 2016; Paquet et al., 2017). Inhibitors such as MMV390048 and UCT943 target the ATP-binding pocket of the enzyme, disrupting the formation of the plasma membrane around daughter merozoites and effectively halting parasite replication (Paquet et al., 2017; Le Manach et al., 2018). While these drugs show potent antiplasmodial activity, achieving high selectivity over the human ortholog is a significant challenge in drug development (McNamara et al., 2013). Furthermore, safety concerns such as potential teratotoxicity have been identified in preclinical studies for some inhibitors in this class (ResearchGate, 2022).

Other names

PvPI4KPvPI4KIIIbetaPhosphatidylinositol 4-kinase type III beta1-phosphatidylinositol 4-kinasePvPI4KIIIb

ATP-competitive inhibition of phosphatidylinositol 4-kinase beta, leading to depletion of phosphatidylinositol 4-phosphate (PI4P) pools and subsequent disruption of Rab11A-mediated membrane trafficking and cytokinesis (McNamara et al., 2013; Paquet et al., 2017).