Table 1.
List of host-targeting compounds with known anti-Plasmodium activity
| Compound | Target | Target type | Proposed mechanism | Ref. |
|---|---|---|---|---|
| K252a | c-MET and other kinases | protein kinase | inhibits kinase activity of c-Met and other tyrosine kinases | Carrolo et al.18 |
| Blockers of lipid transport (BLTs) | scavenger receptor (SR)-B1 | lipoprotein receptor | inhibits SR-B1-mediated selective uptake of lipids from high-density lipoproteins | Rodrigues et al.19 |
| Nutlin-3 | MDM2 | E3 ubiquitin-protein ligase | prevents degradation of p53, promotes lipid peroxidation in infected hepatocytes | Kaushansky et al.20 |
| Serdemetan | MDM2 | E3 ubiquitin-protein ligase | minimizes degradation of p53, eliminate Plasmodium-infected hepatocytes | Douglass et al.21 |
| SB505124 | TGF-β receptor 1 | protein kinase | inhibits the enzymatic activity of kinases involved in multiple cellular processes | Arang et al.22 |
| Auphen | AQP3 | membrane protein | selectively and irreversibly inhibits glycerol transport by AQP3; effective against both liver and blood stages and against multiple human malarias | Posfai et al.23 |
| Brefeldin A | COPI | coatomer protein complex | blocks host intracellular protein trafficking | Raphemot et al.24 |
| Golgicide A | GBF1 | guanine nucleotide exchange factor | blocks host intracellular protein trafficking | Raphemot et al.24 |
| ABT-737, obatoclax | Bcl-2 family proteins | B cell lymphoma 2 family proteins | overcomes apoptotic block placed by parasites, eliminates Plasmodium-infected hepatocytes | Douglass et al.,21 Kaushansky et al.25 |
| PP1 | Src family kinases | protein kinase | inhibits negative regulation of endothelial permeability by Src-family kinases, mediates dissociation of vascular endothelial (VE)-cadherin and redistribution of ZO-1 | Kaushansky et al.,25 Gillrie et al.26 |
| Fasudil | Rho-associated protein kinase | protein kinase | decreases nuclear factor (NF)-κB activation and endothelial cell apoptosis, restores endothelial barrier integrity via rho-kinase signaling pathway | Gillrie et al.,26 Taoufiq et al.27 |
| Imatinib | receptor tyrosine kinases | protein kinase | inhibits erythrocyte band 3 phosphorylation, preventing parasite egress | Sicard et al.,28 Kesely et al.29 |
| PHA-665752 | c-MET | protein kinase | inhibits host c-MET activation during intra-erythrocytic development | Adderley et al.30 |
| Crizotinib | c-MET/Alk | protein kinase | inhibits host c-MET activation during intra-erythrocytic development | Adderley et al.30 |
| SB-590885 | B-Raf | protein kinase | inhibits host B-Raf activation, which halts parasite development during intra-erythrocytic ring stage development | Adderley et al.30 |
| IPA-3 | PAK1 | protein kinase | inhibits host MEK1 activation during intra-erythrocytic development | Sicard et al.28 |
| U-0126 | MEK1/2 | protein kinase | inhibits MEK1/2 activation during intra-erythrocytic development | Sicard et al.28 |
| Propranolol | heterotrimeric G protein (Gs) | G proteins | blocks merozoite invasion of erythrocytes and blood-stage growth | Murphy et al.31 |
| Erastin | SLC7A11 | cystine/glutamate transporter | blocks host SLC7a11-GPX4 pathway to induce lipid peroxidation in Plasmodium-infected hepatocytes | Kain et al.32 |