PBT 1033 (PBT 2) is an orally active copper/zinc ionophore. PBT 1033 restores cognition in mouse models of Alzheimer's disease (AD). PB 1033 also has antibacterial activity against Gram-positive bacteria[1][2].
PB 1033 displays antibacterial activity against S. uberis, with a MIC value of 14.5 μM[2].
PBT2 (1, 3 and 7.5 μM, 6 h) protects neurons against glutamate-induced excitotoxicity[3].
PBT2 (10 μM, 1 or 6 h) reduces NMDAR-mediated Ca2+ flux in mouse cortical neurons[3].
PBT2 (0-10 μM, 1 h) increases GSK3α/β phosphorylation in SH-SY5Y cells[4].
PBT2 (20 μM, 1 h) prevents the formation of Zn-induced protease resistant Aβ aggregates[5].
Western Blot Analysis[4]
| Cell Line: | SH-SY5Y cells |
| Concentration: | 0-10 μM |
| Incubation Time: | 1 h |
| Result: | Increased in cellular levels of GSK3α/β phosphorylated at the inhibitory serine 21/9 residue (ser21/9 on GSK3α/β). |
PBT 1033 (30 mg/kg/d, p.o., 11 days) restores biochemical substrates of learning/memory in a mouse model of alzheimer's disease[5].
| Animal Model: | Female Tg2576 mice[5] |
| Dosage: | 30 mg/kg/d |
| Administration: | Oral administration, 11 days |
| Result: | Increased hippocampal apical spine density, basal spine density. |
[1]. Faux NG, et al. PBT2 rapidly improves cognition in Alzheimer's Disease: additional phase II analyses. J Alzheimers Dis. 2010;20(2):509-16.
[2]. Harbison-Price N, et al. Multiple Bactericidal Mechanisms of the Zinc Ionophore PBT2. mSphere. 2020 Mar 18;5(2):e00157-20.
[3]. Johanssen T, et al. PBT2 inhibits glutamate-induced excitotoxicity in neurons through metal-mediated preconditioning. Neurobiol Dis. 2015 Sep;81:176-85.
[4]. Crouch PJ, et al. The Alzheimer's therapeutic PBT2 promotes amyloid-β degradation and GSK3 phosphorylation via a metal chaperone activity. J Neurochem. 2011 Oct;119(1):220-30.
[5]. Adlard PA, et al. Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer's disease. PLoS One. 2011 Mar 11;6(3):e17669.