PBT 1033 (PBT 2) is an orally bioactive copper/zinc ionophore. PBT 1033 restores cognitive abilities in mice in a mouse model of AD/Alzheimer's disease. PB 1033 also has antimicrobial property against Gram-positive (Gram+) bacteria.

Physicochemical Properties

Molecular Formula	C12H12CL2N2O
Molecular Weight	271.14
Exact Mass	270.032
CAS #	747408-78-2
PubChem CID	10016012
Appearance	Light yellow to brown solid powder
Density	1.4±0.1 g/cm3
Boiling Point	367.8±37.0 °C at 760 mmHg
Flash Point	176.2±26.5 °C
Vapour Pressure	0.0±0.9 mmHg at 25°C
Index of Refraction	1.654
LogP	3.51
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Heavy Atom Count	17
Complexity	265
Defined Atom Stereocenter Count	0
SMILES	C1C(Cl)=C(C2=C(C=CC(CN(C)C)=N2)C=1Cl)O
InChi Key	YZPOQCQXOSEMAZ-UHFFFAOYSA-N
InChi Code	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
Chemical Name	5,7-dichloro-2-[(dimethylamino)methyl]quinolin-8-ol
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	PB 1033 exhibits antimicrobial activity directed against S. uberis, possessing a 14.5 μM MIC value [2]. NEUROSCITOtoxicity caused by glutamate is prevented by PBT2 (1, 3 and 7.5 μM, 6 h)[3]. NMDAR-mediated Ca2+ flux in mouse cortical neurons is decreased by PBT2 (10 μM, 1 or 6 h)[3]. In SH-SY5Y cells, GSK3α/β phosphorylation is increased by PBT2 (0-10 μM, 1 h)[4]. Zn-induced protease-resistant Aβ aggregates are inhibited from forming by PBT2 (20 μM, 1 h)[5].
ln Vivo	In a mouse model of Alzheimer's disease, PBT 1033 (30 mg/kg/d, po, 11 days) restores the biochemical substrates of learning and memory[5].
Cell Assay	Western Blot Analysis[4] Cell Types: SH-SY5Y cells Tested Concentrations: 0-10 μM Incubation Duration: 1 h Experimental Results: Increased in cellular levels of GSK3α/β phosphorylated at the inhibitory serine 21/9 residue (ser21/9 on GSK3α/β).
Animal Protocol	Animal/Disease Models: Female Tg2576 mice[5] Doses: 30 mg/kg/d Route of Administration: Oral administration, 11 days Experimental Results: Increased hippocampal apical spine density, basal spine density.
References	[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.
Additional Infomation	Drug Indication Investigated for use/treatment in alzheimer's disease.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (368.81 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.6881 mL	18.4407 mL	36.8813 mL
	5 mM	0.7376 mL	3.6881 mL	7.3763 mL
	10 mM	0.3688 mL	1.8441 mL	3.6881 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.