Plasmodium falciparum hexose transporter 1 (PfHT1)

Plasmodium falciparum hexose transporter 1 (PfHT1) is the primary protein responsible for the uptake of glucose and other hexoses in the malaria parasite (NIH, 2021). As P. falciparum relies exclusively on glycolysis for energy during its blood-stage infection, PfHT1 is essential for its survival and proliferation (PNAS, 2021). The transporter belongs to the Major Facilitator Superfamily (MFS) and functions as a uniporter that moves glucose down its concentration gradient (UniProt). Inhibition of PfHT1 leads to "selective starvation" of the parasite, making it a highly attractive target for novel antimalarial therapies, especially against drug-resistant strains (Frontiers in Pharmacology, 2022). Small-molecule inhibitors like C3361 and its derivatives target a unique cryptic binding pocket in PfHT1, ensuring high selectivity over human glucose transporters such as GLUT1 and GLUT3 (Jiang et al., 2020). This selectivity is critical to avoid disrupting host glucose homeostasis and causing side effects like hypoglycemia (PLOS One, 2022). Ongoing research focuses on dual orthosteric-allosteric inhibitors to enhance potency and overcome potential resistance mechanisms (IEEE, 2025). PfHT1 is considered a validated target because its genetic deletion is lethal to the parasite in the intraerythrocytic stage (Malaria World, 2021). The protein's structure has been resolved in various states, facilitating structure-based drug design for next-generation antimalarials (ResearchGate, 2022).

Other names

PfHTHexose transporter 1Glucose transporter 1PF3D7_0204700Parasite hexose transporter

Inhibition of glucose uptake leading to parasite starvation and death