Mechanisms of PfDNMT2 inhibition and PfATP6-mediated resistance to the antimalarial candidate SC83288 in Plasmodium falciparum - PubMed
3 days ago
- #antimalarial
- #drug resistance
- #Plasmodium falciparum
- SC83288 is a promising antimalarial candidate effective against drug-resistant Plasmodium falciparum.
- SC83288 disrupts blood-stage development by blocking DNA replication and arresting karyokinesis.
- PfDNMT2, a DNA and tRNAAsp methyltransferase, is identified as the primary molecular target of SC83288.
- Resistance to SC83288 arises through mutations in PfATP6, a SERCA-type Ca²⁺ ATPase, which relocates the drug away from its nuclear targets.
- The resistance mechanism involving PfATP6 mutations carries a significant fitness cost, limiting its spread.
- SC83288's unique resistance profile and high fitness cost enhance its potential as a clinical development candidate.