THK5351 can be used as a radioactive tracer after being radioactively labeled to study tau pathological imaging in the brain.

Physicochemical Properties

Molecular Formula	C18H18FN3O2
Molecular Weight	327.352827548981
Exact Mass	327.138
CAS #	1707147-26-9
Related CAS #	THK5351 (R enantiomer);2101218-44-2
PubChem CID	91936858
Appearance	Light yellow to yellow solid powder
Density	1.3±0.1 g/cm3
Boiling Point	561.5±50.0 °C at 760 mmHg
Flash Point	293.4±30.1 °C
Vapour Pressure	0.0±1.6 mmHg at 25°C
Index of Refraction	1.642
LogP	2.65
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	24
Complexity	387
Defined Atom Stereocenter Count	1
SMILES	CNC1=NC=C(C=C1)C2=NC3=C(C=C2)C=C(C=C3)OC[C@@H](CF)O
InChi Key	DLVXFZWSPCOWSN-CQSZACIVSA-N
InChi Code	InChI=1S/C18H18FN3O2/c1-20-18-7-3-13(10-21-18)17-5-2-12-8-15(4-6-16(12)22-17)24-11-14(23)9-19/h2-8,10,14,23H,9,11H2,1H3,(H,20,21)/t14-/m1/s1
Chemical Name	(2S)-1-fluoro-3-[2-[6-(methylamino)pyridin-3-yl]quinolin-6-yl]oxypropan-2-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	One important neuropathological substrate that plays a key role in the pathophysiology of neurodegenerative diseases like Alzheimer's disease (AD) is aggregated tau protein. 18F-THK5351 exhibits a high degree of affinity (Kd=2.9 nM; maximum number of binding sites = 368.3 pmol/g tissue) for Alzheimer's disease hippocampus homogenate. It quickly separates from the white matter tissue. The quantity of tau deposition in tissues is correlated with the amount of THK5351 bound [1].
ln Vivo	In mice, THK5351 shows no defluorination and good pharmacokinetics. 18F-THK5351 is injected intravenously, enters the brain right away, and leaves the brain quickly. No animals died at doses of 0.1 or 1 mg/kg, and clinical observation, body weight measurements, and pathological examinations did not reveal any treatment-related changes in any of the animals [1]. PSP patients' brain sections autoradiographically reveal that [3H]THK-5351 binds to tau deposits with extreme selectivity. PSP patients had significantly higher tracer retention in the globus pallidus and midbrain [2], despite not exhibiting significant [18F]THK-5351 retention in the temporal cortex.
References	[1]. 18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease. J Nucl Med. 2016 Feb;57(2):208-14. [2]. Tau imaging with [18 F]THK-5351 in progressive supranuclear palsy. Eur J Neurol. 2017 Jan;24(1):130-136.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~152.74 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.64 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0548 mL	15.2742 mL	30.5483 mL
	5 mM	0.6110 mL	3.0548 mL	6.1097 mL
	10 mM	0.3055 mL	1.5274 mL	3.0548 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.