GSK2556286   Click here for help

GtoPdb Ligand ID: 13078

Synonyms: GSK286
Compound class: Synthetic organic
Comment: GSK2556286 is a substituted 4-aryloxypiperidine identified from a screen of compounds that inhibit intracellular growth of Mycobacterium tuberculosis in human macrophage-like differentiated monocytes (THP-1 cell line) [2]. It has a novel cholesterol-dependent mechanism of action, with recent studies establishing it as an agonist of mycobacterial Rv1625c, a membrane-bound adenylyl cyclase [1-2]. GSK2556286 is under clinical development as a potential treatment for tuberculosis (TB).
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 6
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 70.67
Molecular weight 329.39
XLogP 1.06
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 CC1=CC=CC(=C1C)OC2CCN(CC2)CC3=CC(=O)NC(=O)N3
Isomeric SMILES CC1=C(C(=CC=C1)OC2CCN(CC2)CC3=CC(=O)NC(=O)N3)C
InChI InChI=1S/C18H23N3O3/c1-12-4-3-5-16(13(12)2)24-15-6-8-21(9-7-15)11-14-10-17(22)20-18(23)19-14/h3-5,10,15H,6-9,11H2,1-2H3,(H2,19,20,22,23)
InChI Key AZOFJHATIPDIER-UHFFFAOYSA-N
References
1. Brown KL, Wilburn KM, Montague CR, Grigg JC, Sanz O, Pérez-Herrán E, Barros D, Ballell L, VanderVen BC, Eltis LD. (2023)
Cyclic AMP-Mediated Inhibition of Cholesterol Catabolism in Mycobacterium tuberculosis by the Novel Drug Candidate GSK2556286.
Antimicrob Agents Chemother, 67 (1): e0129422. [PMID:36602336]
2. Nuermberger EL, Martínez-Martínez MS, Sanz O, Urones B, Esquivias J, Soni H, Tasneen R, Tyagi S, Li SY, Converse PJ et al.. (2022)
GSK2556286 Is a Novel Antitubercular Drug Candidate Effective In Vivo with the Potential To Shorten Tuberculosis Treatment.
Antimicrob Agents Chemother, 66 (6): e0013222. [PMID:35607978]