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

SQ-109 is commercially available from our sponsors

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 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

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 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

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/)
No information available.
Summary of Clinical Use Click here for help
Phase 2 clinical trials have been completed to evaluate SQ-109 as a treatment for tuberculosis but recruitment to NCT01785186 was terminated early because the drug did not meet prespecified efficacy thresholds [1].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
In mycobacteria, SQ-109 disrupts cell wall assembly and shown to inhibit MmpL3, a member of the resistance-nodulation-division (RND) transporter superfamily, by binding inside the transmembrane domain [5-6].
The Plasmodium genome has no predicted direct homologue of MmpL3 and SQ-109 does not inhibit P. falciparum Niemann-Pick type C1-related protein (PfNCR1), a member of the RND superfamily [4]. An alternative molecular target, the A subunit of P. falciparum V-type proton ATPase (PfvapA, see here for our target page for the D subunit), has been identified using reverse genetics but further studies are required to validate this target [4].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01785186 Evaluation of SQ109, High-dose Rifampicin, and Moxifloxacin in Adults With Smear-positive Pulmonary TB in a MAMS Design Phase 2 Interventional Ludwig-Maximilians - University of Munich 1
NCT01218217 Early Bactericidal Activity (EBA) of SQ109 in Adult Subjects With Pulmonary TB Phase 2 Interventional Ludwig-Maximilians - University of Munich