SQ-109   Click here for help

GtoPdb Ligand ID: 7997

Synonyms: MMV687273 | SQ 109 | SQ109
Antimalarial Ligand
Compound class: Synthetic organic
Comment: SQ-109 is a [1,2]-diamine-based ethambutol analogue included in the Medicines for Malaria Pandemic Response Box (MMV PRB). Functionally, it inhibits Mycobacterial membrane protein large 3 (MmpL3) and has advanced to clinical evaluation for the treatment of tuberculosis [5].

The compound also has antimalarial activity. 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 2
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 24.06
Molecular weight 330.3
XLogP 5.22
No. Lipinski's rules broken 1
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 CC(=CCNCCNC1C2CC3CC1CC(C2)C3)CCC=C(C)C
Isomeric SMILES C/C(=C\CNCCNC1C2CC3CC1CC(C2)C3)/CCC=C(C)C
InChI InChI=1S/C22H38N2/c1-16(2)5-4-6-17(3)7-8-23-9-10-24-22-20-12-18-11-19(14-20)15-21(22)13-18/h5,7,18-24H,4,6,8-15H2,1-3H3/b17-7+
InChI Key JFIBVDBTCDTBRH-REZTVBANSA-N
Bioactivity Comments
SQ-109 has activity against both drug susceptible and multidrug resistant strains of M. tuberculosis (MIC of 0.7-1.56 μM in vitro) [3].
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
squalene synthase Hs Inhibitor Inhibition 6.1 pKi - 2
⤷ pKi 6.1 (Ki 7.4x10-7 M) [2]
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
Unknown MOA 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 late stage (IV–V) gametocyte assay - - 7.0 pIC50 - 4
⤷ pIC50 7.0 (IC50 1.05x10-7 M) [4]
Unknown MOA 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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 Parasite exflagellation assay - - - - - 4
⤷ ≥80% inhibition of male gamete exflagellation following 48hour exposure of mature gametocytes to 2µM SQ-109 [4]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)