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
References
1. Boeree MJ, Heinrich N, Aarnoutse R, Diacon AH, Dawson R, Rehal S, Kibiki GS, Churchyard G, Sanne I, Ntinginya NE et al.. (2017)
High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial.
Lancet Infect Dis, 17 (1): 39-49. [PMID:28100438]
2. Lin FY, Liu YL, Li K, Cao R, Zhu W, Axelson J, Pang R, Oldfield E. (2012)
Head-to-head prenyl tranferases: anti-infective drug targets.
J Med Chem, 55 (9): 4367-72. [PMID:22486710]
3. Protopopova M, Hanrahan C, Nikonenko B, Samala R, Chen P, Gearhart J, Einck L, Nacy CA. (2005)
Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines.
J Antimicrob Chemother, 56 (5): 968-74. [PMID:16172107]
4. Reader J, van der Watt ME, Taylor D, Le Manach C, Mittal N, Ottilie S, Theron A, Moyo P, Erlank E, Nardini L et al.. (2021)
Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box.
Nat Commun, 12 (1): 269. [PMID:33431834]
5. Tahlan K, Wilson R, Kastrinsky DB, Arora K, Nair V, Fischer E, Barnes SW, Walker JR, Alland D, Barry 3rd CE et al.. (2012)
SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis.
Antimicrob Agents Chemother, 56 (4): 1797-809. [PMID:22252828]
6. Zhang B, Li J, Yang X, Wu L, Zhang J, Yang Y, Zhao Y, Zhang L, Yang X, Yang X et al.. (2019)
Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target.
Cell, 176 (3): 636-648.e13. [PMID:30682372]