(+)-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.
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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.

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View interactive charts of activity data across species
2D Structure
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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.

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Physico-chemical Properties
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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.

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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
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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.

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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
References
1. Gaur AH, McCarthy JS, Panetta JC, Dallas RH, Woodford J, Tang L, Smith AM, Stewart TB, Branum KC, Freeman 3rd BB et al.. (2020)
Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4 inhibitor SJ733: a first-in-human and induced blood-stage malaria phase 1a/b trial.
Lancet Infect Dis, 20 (8): 964-975. [PMID:32275867]
2. Jiménez-Díaz MB, Ebert D, Salinas Y, Pradhan A, Lehane AM, Myrand-Lapierre ME, O'Loughlin KG, Shackleford DM, Justino de Almeida M, Carrillo AK et al.. (2014)
(+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium.
Proc Natl Acad Sci USA, 111 (50): E5455-62. [PMID:25453091]
3.  MMV Annual Report 2018, Chapter 7, R&D platforms and discovery.
Accessed on 27/01/2020. Modified on 27/01/2020. https://www.mmv.org/sites/default/files/uploads/docs/publications/2018/MMV_AR2018_Chapter7.pdf