(+)-SJ733   Click here for help

GtoPdb Ligand ID: 9723

Synonyms: (+)-SJ000557733 | (+)-SJ557733
Antimalarial Ligand
Compound class: Synthetic organic
Comment: (+)-SJ733 is the optimized lead for the dihydroisoquinolones (DHIQ), a novel chemotype with antimalarial activity [2].
The (+)-enantiomer, shown here, has a significantly higher antimalarial potency [2].

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 86.09
Molecular weight 468.12
XLogP 3.8
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES N#Cc1cc(ccc1F)NC(=O)C1c2ccccc2C(=O)N(C1c1cccnc1)CC(F)(F)F
Isomeric SMILES N#Cc1cc(ccc1F)NC(=O)[C@H]1c2ccccc2C(=O)N([C@@H]1c1cccnc1)CC(F)(F)F
InChI InChI=1S/C24H16F4N4O2/c25-19-8-7-16(10-15(19)11-29)31-22(33)20-17-5-1-2-6-18(17)23(34)32(13-24(26,27)28)21(20)14-4-3-9-30-12-14/h1-10,12,20-21H,13H2,(H,31,33)/t20-,21+/m0/s1
InChI Key VKCPFWKTFZAOTO-LEWJYISDSA-N
Guide to Malaria Pharmacology Comments
(+)-SJ733 is equally potent against all developmental forms of the asexual blood stage parasite and also has potential for transmission blockade [2]. The compound was under clinical development as the fast clearance component of a single-exposure radical cure and prophylaxis (SERCaP) antimalarial drug but is no longer in the Medicines for Malaria (MMV) portfolio after it was found to have lower concentrations in humans than expected [3]. A back-up series, that has been informed by (+)-SJ733, is being developed by the University of Kentucky (see compound 1a [WO2021204952A1] for more details).

Potential Target/Mechanism of Action: Evidence from genetic experiments indicates that Plasmodium non-SERCA-type Ca2+-transporting P-ATPase (PfATP4) may be the relevant molecular target [2]. Further information about possible mechanistic insights is provided under the Clinical data tab.
Target Candidate Profiles
Profile Intended Use Target Stage Comment References
TCP-5 transmission reduction gametocytes 2
TCP-1 reduce parasite burden asexual blood stages 2