sutidiazine   Click here for help

GtoPdb Ligand ID: 10024

Synonyms: AZ13721412 | MMV674253 | ZY19489
Antimalarial Ligand
Compound class: Synthetic organic
Comment: MMV253 is the clinical lead for the triaminopyrimidines (TAPs), a novel class of antimalarial compounds identified from a phenotypic screen [1].

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

The chemical structure of MMV253 matches the INN sutidiazine (proposed INN list 129; August 2023).
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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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 8
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 87.03
Molecular weight 465.28
XLogP 3.98
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CC1CN(CCN1C)c1cnc(nc1Nc1cc(n(n1)C)C)Nc1nc(C)c(c(c1)C1CC1)F
Isomeric SMILES C[C@@H]1CN(CCN1C)c1cnc(nc1Nc1cc(n(n1)C)C)Nc1nc(C)c(c(c1)C1CC1)F
InChI InChI=1S/C24H32FN9/c1-14-10-21(31-33(14)5)28-23-19(34-9-8-32(4)15(2)13-34)12-26-24(30-23)29-20-11-18(17-6-7-17)22(25)16(3)27-20/h10-12,15,17H,6-9,13H2,1-5H3,(H2,26,27,28,29,30,31)/t15-/m1/s1
InChI Key HKPQFVAUXAZCDY-OAHLLOKOSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
TAPs lack appreciable activity against the sexual forms or liver stages of the parasite (IC50 >1μM) [1]. MMV253 has an in vitro parasite reduction ratio (PRR) of >4-log after 48 hours of exposure and is similar to that of chloroquine [1].
Whole organism assay data
Key to terms and symbols Click on species/strain names for details Click column headers to sort
MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Plasmodium falciparum V-type proton ATPase subunit D PfNF54

Plasmodium falciparum NF54

P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands.
PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine.
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 Parasite growth inhibition assay - - 8.1 pIC50 - 1
⤷ pIC50 8.1 (IC50 9x10-9 M) SYBR Green assay [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum V-type proton ATPase subunit D PfK1

Plasmodium falciparum K1

P. falciparum strain K1 (PfK1) was isolated in Kanchanaburi, Thailand in 1979.
PfK1 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be a multidrug-resistant strain.
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 Parasite growth inhibition assay - - 7.8 pIC50 - 1
⤷ pIC50 7.8 (IC50 1.5x10-8 M) SYBR Green assay [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)