DSM705   Click here for help

GtoPdb Ligand ID: 11554

Synonyms: compound 79
PDB Ligand Antimalarial Ligand
Compound class: Synthetic organic
Comment: DSM705 is a lead from a pyrrole-based series of antimalarial compounds that inhibit P. falciparum dihydroorotate dehydrogenase (PfDHODH) [1]. This series of PfDHODH inhibitors could provide a potential backup candidate, with an alternative scaffold, to the clinical lead DSM265.
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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 7
Topological polar surface area 99.35
Molecular weight 404.16
XLogP 3.06
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 O=C(c1[nH]cc(c1C)C1(CC1)c1ccc(nc1)C(F)(F)F)N[C@@H](c1ncn[nH]1)C
Isomeric SMILES O=C(c1[nH]cc(c1C)C1(CC1)c1ccc(nc1)C(F)(F)F)N[C@@H](c1ncn[nH]1)C
InChI InChI=1S/C19H19F3N6O/c1-10-13(8-24-15(10)17(29)27-11(2)16-25-9-26-28-16)18(5-6-18)12-3-4-14(23-7-12)19(20,21)22/h3-4,7-9,11,24H,5-6H2,1-2H3,(H,27,29)(H,25,26,28)/t11-/m1/s1
InChI Key JUBPRXDFKLPILK-LLVKDONJSA-N
Selectivity at enzymes
Key to terms and symbols Click on species/strain names for details Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
dihydroorotate dehydrogenase (quinone) Hs Inhibitor Inhibition <4.0 pIC50 - 1
⤷ pIC50 <4.0 (IC50 >1x10-4 M) [1]
Description: Steady-state kinetic analysis.
Selectivity at other protein targets
Key to terms and symbols Click on species/strain names for details Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Plasmodium falciparum dihydroorotate dehydrogenase Pv

Plasmodium vivax

P. vivax (Pv) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pv is the second most common cause of malaria in humans, after P. falciparum, and is prevalent in Southeast Asia and Latin America. Pv has a dormant liver stage that can reactivate and lead to clinical symptoms.
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 Inhibitor Inhibition 7.3 pIC50 - 1
⤷ pIC50 7.3 (IC50 5.2x10-8 M) [1]
Description: Steady-state kinetic analysis.
Plasmodium falciparum dihydroorotate dehydrogenase Pf

Plasmodium falciparum

P. falciparum (Pf) is one of five protozoan parasite species of the genus Plasmodium that cause malaria in humans. Pf is responsible for the majority of malaria related deaths and is the most prevalent species in sub-Saharan Africa.
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 Inhibitor Inhibition 7.0 pIC50 - 1
⤷ pIC50 7.0 (IC50 9.5x10-8 M) [1]
Description: Steady-state kinetic analysis.
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 dihydroorotate dehydrogenase 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 - - 7.9 pEC50 - 1
⤷ pEC50 7.9 (EC50 1.2x10-8 M) SYBR Green I assay (72h) [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Plasmodium falciparum dihydroorotate dehydrogenase Pb

Plasmodium berghei

P. berghei (Pb) is a malaria parasite that infects mammals other than humans with the natural mammalian host being the thicket rat (G. surdaster) from Central Africa.
Pb is used in rodent model studies of malaria.
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 Parasite liver stage assay - - 7.9 pEC50 - 1
⤷ pEC50 7.9 (EC50 1.3x10-8 M) Luciferase bioluminescence (Pbluc) assay to measure sporozoite invasion into HepG2 liver cells (prophylactic activity) [1]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)