| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
A-1070722 is a potent, selective, and brain-penetrant inhibitor of Glycogen Synthase Kinase 3 (GSK-3). It has a high affinity for both GSK-3α and GSK-3β isoforms with a Ki of 0.6 nM. [1]
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| ln Vitro |
A-1070722 shows >50-fold selectivity for GSK-3 over a panel of other kinases. [1]
It decreased tau phosphorylation and protected rat primary cortical neurons against β-amyloid and glutamate challenge in vitro, supporting its neuroprotective potential and confirming its ability to engage the target in a cellular context. [1] |
| ln Vivo |
The carbon-11 labeled version, [¹¹C]A-1070722, was evaluated as a Positron Emission Tomography (PET) radiotracer in vervet/African green monkeys. [1]
PET imaging showed that [¹¹C]A-1070722 penetrated the blood-brain barrier and accumulated in the brain. The distribution was relatively heterogeneous, with the highest radioactivity uptake observed in the frontal cortex, followed by the parietal cortex and anterior cingulate. Lower uptake was found in the caudate, putamen, and thalamus. This distribution pattern aligns with the known postmortem distribution of GSK-3β in the human brain. [1] The radiotracer also showed significant binding to both cortical and cerebellar white matter regions. [1] The time-activity curves indicated that the radiotracer did not reach equilibrium binding in all brain regions within the 90-120 minute scan duration. [1] |
| Animal Protocol |
PET imaging studies were conducted in fasted adult male vervet monkeys (Chlorocebus aethiops sabaeus). [1]
Animals were initially immobilized with ketamine (10 mg/kg, intramuscular) and maintained under anesthesia with 1.5–2.0% isoflurane delivered via an endotracheal tube. Body temperature was maintained at 37°C. [1] [¹¹C]A-1070722 was formulated in saline with 10% ethanol. [1] The radiotracer was administered as a single intravenous bolus injection over 30 seconds. The injected dose was 407 ± 80 MBq. [1] Emission PET data were collected for 90 minutes (in 2 scans) or 120 minutes (in 1 scan) in 3D mode following a 10-minute transmission scan. [1] An arterial line was placed for serial blood sampling to measure the input function and for metabolite analysis. [1] |
| ADME/Pharmacokinetics |
Following intravenous injection in monkeys, the levels of radioactivity in arterial blood and plasma peaked at 2 minutes post-injection and were subsequently cleared rapidly. [1]
Metabolite analysis of plasma samples showed the presence of polar metabolites. The percentages of unmetabolized parent [¹¹C]A-1070722 in plasma were 92.5 ± 0.85% at 2 minutes, 89.0 ± 1% at 4 minutes, 51.9 ± 6.9% at 12 minutes, 45.1 ± 12.9% at 30 minutes, 35.6 ± 15% at 60 minutes, and 20.1 ± 9.5% at 90 minutes. [1] The total regional distribution volume (VT) of [¹¹C]A-1070722 in the brain was calculated using metabolite-corrected arterial input functions and a two-compartment model or graphical (Logan) analysis. The highest VT values were found in cortical regions (e.g., frontal lobe, parietal lobe, anterior cingulate cortex) and the cerebellum. [1] |
| References | |
| Additional Infomation |
A-1070722 (unlabeled) is a small molecule with a calculated partition coefficient (ClogP) of 3.2, which is favorable for crossing the blood-brain barrier. [1]
Its radiolabeled analog [¹¹C] A-1070722 was synthesized by O-[¹¹C]methylation of a demethylated precursor (phenolate) in DMF with [¹¹C]methyl iodide and then in the presence of NaOH for PET imaging. The radiochemical yield was 40 ± 5%, and the specific activity was 88.8 ± 15 GBq/μmol. [1] This study shows that the A-1070722 structural framework has the potential to develop brain imaging agents targeting GSK-3. However, the observed low total volume of distribution (VT) value indicates a low target concentration or poor tracer kinetics in normal monkey brains. [1] |
| Molecular Formula |
C17H13F3N4O2
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|---|---|
| Molecular Weight |
362.305933713913
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| Exact Mass |
362.099
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| CAS # |
1384424-80-9
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| PubChem CID |
49830684
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
412.5±45.0 °C at 760 mmHg
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| Flash Point |
203.3±28.7 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.653
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| LogP |
4.36
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
491
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VQPBIJGXSXEOCU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H13F3N4O2/c1-26-10-5-6-11-12(7-8-21-13(11)9-10)22-16(25)24-15-4-2-3-14(23-15)17(18,19)20/h2-9H,1H3,(H2,21,22,23,24,25)
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| Chemical Name |
1-(7-methoxyquinolin-4-yl)-3-[6-(trifluoromethyl)pyridin-2-yl]urea
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~83.33 mg/mL (~230.00 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7601 mL | 13.8003 mL | 27.6007 mL | |
| 5 mM | 0.5520 mL | 2.7601 mL | 5.5201 mL | |
| 10 mM | 0.2760 mL | 1.3800 mL | 2.7601 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.
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