An Update on Development of Small-Molecule Plasmodial Kinase Inhibitors

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 21; p. 5182
• Main Authors: Moolman, Chantalle, Sluis, Rencia van der, Beteck, Richard M, Legoabe, Lesetja J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07-11-2020; MDPI
• Subjects: Animals; Antimalarial agents; Antimalarials - pharmacology; Calcium - metabolism; Casein Kinase I - metabolism; Chemoprotection; Coronaviruses; COVID-19; Culicidae; Disease control; Disease transmission; Drug Design; Drug development; Drug Discovery - trends; Drug Resistance; Drugs; Enzyme inhibitors; Erythrocytes; Glycogen Synthase Kinase 3 - metabolism; Humans; Imidazoles - pharmacology; Inhibitory Concentration 50; kinase inhibitors; Kinases; Life Cycle Stages - drug effects; Malaria; Malaria - drug therapy; MAP Kinase Signaling System; Parasites; Phosphotransferases - chemistry; Plasmodium; Plasmodium - drug effects; Plasmodium - enzymology; Protein Kinase Inhibitors - pharmacology; Pyridines - pharmacology; Review; Vector-borne diseases; Plasmodium; antimalarial agents; kinase inhibitors; kinases; malaria
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25215182

Malaria control relies heavily on the small number of existing antimalarial drugs. However, recurring antimalarial drug resistance necessitates the continual generation of new antimalarial drugs with novel modes of action. In order to shift the focus from only controlling this disease towards elimination and eradication, next-generation antimalarial agents need to address the gaps in the malaria drug arsenal. This includes developing drugs for chemoprotection, treating severe malaria and blocking transmission. Plasmodial kinases are promising targets for next-generation antimalarial drug development as they mediate critical cellular processes and some are active across multiple stages of the parasite's life cycle. This review gives an update on the progress made thus far with regards to plasmodial kinase small-molecule inhibitor development.