| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
THK5351 targets tau protein aggregates, including neurofibrillary tangles, which are a hallmark of Alzheimer's disease and other tauopathies. It binds with high affinity to paired helical filaments of tau. It may also have some affinity for monoamine oxidase B (MAO-B), which contributes to its binding signal.
|
|---|---|
| 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].
In vitro, THK5351 shows high affinity for tau aggregates, with Ki values in the low nanomolar range. It has been characterized in binding assays using brain homogenates from patients with Alzheimer's disease and other tauopathies. It shows selectivity for tau over amyloid-beta. |
| 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.
In vivo, [18F]THK5351 is used for PET imaging of tau pathology in the human brain. It shows increased retention in brain regions known to contain tau aggregates, such as the temporal and frontal lobes. It has been used in clinical studies to track tau progression in Alzheimer's disease and to differentiate tauopathies from other dementias. |
| Enzyme Assay |
In vitro binding assays are performed using brain tissue homogenates from patients with tauopathies. [3H]THK5351 or a related radioligand is used as a tracer. Various concentrations of unlabeled THK5351 are added, and bound radioactivity is measured. Ki values are calculated from competition binding curves.
|
| Cell Assay |
THK5351 binding is characterized in autoradiography studies using brain tissue sections from patients with Alzheimer's disease and control subjects. Sections are incubated with [3H]THK5351, and the distribution of binding is visualized by autoradiography. The binding pattern is compared to tau immunohistochemistry.
|
| Animal Protocol |
Animal studies for THK5351 involve the administration of [18F]THK5351 to rodents or non-human primates. PET imaging is performed, and the biodistribution and clearance of the tracer are evaluated. The specificity of binding is assessed using blocking studies with unlabeled THK5351.
|
| ADME/Pharmacokinetics |
[18F]THK5351 is a small molecule (MW ~462). It has good brain penetration and rapid washout from non-target regions. It is metabolized in the liver and excreted in urine. The half-life of [18F] is 110 minutes, so imaging is performed shortly after injection.
|
| Toxicity/Toxicokinetics |
THK5351 is used as a PET imaging agent at very low doses (microdoses). The radiation exposure from [18F]THK5351 is within acceptable limits for clinical PET imaging. No pharmacological toxicity is expected at the imaging doses used.
|
| References | |
| Additional Infomation |
THK5351 is a research compound used as a PET imaging agent for tau pathology. It is not an approved drug for therapeutic use. It has been used in clinical trials for the imaging of Alzheimer's disease and other tauopathies. It is not commercially available for clinical use.
|
| 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)
|
| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
