JX21108   Click here for help

GtoPdb Ligand ID: 11808

Antimalarial Ligand
Compound class: Synthetic organic
Comment: JX21108 is a selective inhibitor of P. falciparum histone deacetylase 1 (PfHDAC1) that was developed from chemical optimization of quisinostat [1].
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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 5
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 111.51
Molecular weight 432.21
XLogP 1.79
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#Cc1ccc2c(c1)c(C[NH+]1CCC3(C1)CCN(C3)c1ncc(cn1)C(=O)NO)cn2C
Isomeric SMILES Cn1cc(C[NH+]2CCC3(CCN(c4ncc(C(=O)NO)cn4)C3)C2)c2cc(C#N)ccc12
InChI InChI=1S/C23H25N7O2/c1-28-12-18(19-8-16(9-24)2-3-20(19)28)13-29-6-4-23(14-29)5-7-30(15-23)22-25-10-17(11-26-22)21(31)27-32/h2-3,8,10-12,32H,4-7,13-15H2,1H3,(H,27,31)/p+1
InChI Key XYBGCCKUMXSCIP-UHFFFAOYSA-O
Bioactivity Comments
JX21108 demonstrates activity against multiple Plasmodium lifecycle stages. The interaction table below provides data from whole cell assays and gives the antiparasite activity of JX21108 against both the sexual and asexual blood stages. In addition, no sign of liver infection was observed in a P. berghei mouse model using a single 60 mg/kg dose [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 histone deacetylase 1 Pf3D7

Plasmodium falciparum 3D7

P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1).
Pf3D7 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 - - 8.4 pEC50 - 1
⤷ pEC50 8.4 (EC50 3.6x10-9 M) SYBR Green I assay (72 hours) [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum histone deacetylase 1 PfDd2

Plasmodium falciparum Dd2

P. falciparum strain Dd2 (PfDd2) is a clone derived from PfW2, following continuous culture in mefloquine. PfW2 was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy.
PfDd2 can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine, pyrimethamine and mefloquine.
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 Parasite growth inhibition assay - - 8.4 pEC50 - 1
⤷ pEC50 8.4 (EC50 4x10-9 M) SYBR Green I assay (72 hours) [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum histone deacetylase 1 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 gametocyte viability assay - - 7.4 – 8.2 pEC50 - 1
⤷ pEC50 8.2 (EC50 5.9x10-9 M) Parasite late stage (IV) gametocyte assay using luciferase reporter line [1]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
pEC50 7.4 (EC50 3.88x10-8 M) Parasite early stage (II) gametocyte assay using luciferase reporter line [1]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)