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. |
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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] |