PBT2   Click here for help

GtoPdb Ligand ID: 11108

Synonyms: PBT-1033 | PBT-2 | PBT1033
Compound class: Synthetic organic
Comment: PBT2 is an orally administered, safe-in-humans zinc ionophore. Chemically it is an 8-hydroxyquinoline analogue. PBT2 has been classified as a metal-protein attenuating compound (MPAC), and is designed to interfere with zinc ion interactions with proteins.
Antibacterial activity: Whilst not active alone, PBT2 + zinc + antibacterial 'X' acts synergistically to overcome acquired bacterial-resistance to antibacterial 'X' (which can include clinically used antibacterials). This strategy produces activity against antibacterial-resistant Gram-positive pathogens [1].
SARS-CoV-2: Based on evidence from previous studies in MERS-CoV and SARS-CoV-1, zinc modulation (e.g. by PBT2 or disulfiram [4]) has been proposed as a potential mechanism for the prophylaxis/treatment of COVID-19. Altering zinc ion levels is predicted to affect activity of host and/or viral zinc-containing metalloenzymes.
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 1
Rotatable bonds 2
Topological polar surface area 36.36
Molecular weight 270.03
XLogP 2.8
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 CN(Cc1ccc2c(n1)c(O)c(cc2Cl)Cl)C
Isomeric SMILES CN(Cc1ccc2c(n1)c(O)c(cc2Cl)Cl)C
InChI InChI=1S/C12H12Cl2N2O/c1-16(2)6-7-3-4-8-9(13)5-10(14)12(17)11(8)15-7/h3-5,17H,6H2,1-2H3
InChI Key YZPOQCQXOSEMAZ-UHFFFAOYSA-N
References
1. Bohlmann L, De Oliveira DMP, El-Deeb IM, Brazel EB, Harbison-Price N, Ong CY, Rivera-Hernandez T, Ferguson SA, Cork AJ, Phan MD et al.. (2018)
Chemical Synergy between Ionophore PBT2 and Zinc Reverses Antibiotic Resistance.
mBio, 9 (6). DOI: 10.1128/mBio.02391-18 [PMID:30538186]
2. Huntington Study Group Reach2HD Investigators. (2015)
Safety, tolerability, and efficacy of PBT2 in Huntington's disease: a phase 2, randomised, double-blind, placebo-controlled trial.
Lancet Neurol, 14 (1): 39-47. [PMID:25467848]
3. Lannfelt L, Blennow K, Zetterberg H, Batsman S, Ames D, Harrison J, Masters CL, Targum S, Bush AI, Murdoch R et al.. (2008)
Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial.
Lancet Neurol, 7 (9): 779-86. [PMID:18672400]
4. Lin MH, Moses DC, Hsieh CH, Cheng SC, Chen YH, Sun CY, Chou CY. (2018)
Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes.
Antiviral Res, 150: 155-163. [PMID:29289665]