- Guide to PHARMACOLOGY
Synonyms: (+)-SJ000557733 | (+)-SJ557733
Compound class: Synthetic organic
Comment: (+)-SJ733 is the optimized lead for the dihydroisoquinolones (DHIQ), a novel chemotype with antimalarial activity .
The (+)-enantiomer, shown here, has a significantly higher antimalarial potency .
The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.|
|Summary of Clinical Use|
|(+)-SJ733 has completed Phase 1 trials, demonstrating a favourable pharmacokinetic, tolerability, and safety profile combined with rapid parasite clearance .|
|Mechanism Of Action and Pharmacodynamic Effects|
|The exact mechanism of action of (+)-SJ733 is not fully understood but Plasmodium non-SERCA-type Ca2+-transporting P-ATPase (PfATP4) may be the potential target because mutatations in PfATP4 confer resistance to this compound . (+)-SJ733 produces a rapid perturbation of parasitic intracellular Na+ levels, in concurrence with the proposed role of PfATP4 in the regulation of Na+ homeostasis, followed by physical changes in the infected erythrocytes. It has been proposed that host-mediated clearance of infected cells may be responsible for the rapid action of PfATP4 inhibitors .|
|Clinical Trial ID||Title||Type||Source||Comment||References|
|NCT02867059||SJ733 Induced Blood Stage Malaria Challenge Study||Phase 1 Interventional||Medicines for Malaria Venture||1|
|NCT02661373||First-in-Human Study of an Oral Plasmodium Falciparum Plasma Membrane Protein Inhibitor||Phase 1 Interventional||St. Jude Children's Research Hospital||1|