Table 1 |.

Antimalarial targets with clinical validation

Target (systematic name)	Clinical stage	Mechanism of action	Noteworthy inhibitors	Refs.
Cytochrome B; CytB (PF3D7_MIT02300)	Approved (atovaquone)	Subunit of cytochrome bc1 complex; has a critical role in the electron transport chain and ATP production	Atovaquone (Qo site); ELQ-331a (Qi site)	178,179
Haeme	Approved	Haemoglobin degradation is critical to malaria parasite blood-stage growth	Chloroquine, amodiaquine, piperaquine	180
Dihydrofolate reductase–thymidylate synthase; DHFR-TS (PF3D7_0417200)	Approved (pyrimethamine, cycloguanil)	A dual-function enzyme that creates precursors for DNA synthesis	Pyrimethamine, cycloguanil, P218a (DHFR site)	181
Dihydropteroate synthase; DHPS (PF3D7_0810800)	Approved	Catalyzes the last step in folate acid biosynthesis	Sulfadoxine	182
Deoxy-d-xylulose 5-phosphate reductoisomerase; DXR (PF3D7_1467300)	Approved	Catalyzes the non-mevalonate pathway	Fosmidomycin	183
Prolyl tRNA synthetase; PRS (PF3D7_0925300)	Approved	Essential for protein biosynthesis in all replicating parasite stages	Halofuginone	184–186
70S ribosome	Approved	Essential for protein synthesis	Macrolide antibiotics (such as azithromycin)	187
Dihydroorotate dehydrogenase; DHODH (PF3D7_0603300)	Phase II trials	Generates pyrimidine precursors for DNA synthesis	DSM265	81,188–191
PfATPase4; ATP4 (PF3D7_1211900)	Phase II trials	Maintains sodium homeostasis in parasite blood stages	SJ733; cipargamin	62,170, 192–194
Phosphatidylinositol 4-kinase; PI4K (PF3D7_0509800)	Phase II trials	Predicted lipid kinases with an essential role in trafficking	KDU691; MMV390048	93,195–198
Elongation factor 2; eEF2 (PF3D7_1451100)	Phase II trials	ATP-dependent enzyme with a critical role in protein biosynthesis	Cabamiquine (M5717)	142,143,199
Multidrug resistance protein 1; MDR1 (PF3D7_0523000)	Not available	Digestive vacuole membrane-localized ABC transporter	Multiple, including ACT-451840	200

^aCompounds in clinical studies.