| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
hGSK-3β 12 nM (IC50)
GSK-3beta (glycogen synthase kinase-3 beta). SAR502250 is an ATP-competitive inhibitor of human GSK-3beta with an IC50 of 12 nM. It also potently inhibits rodent GSK-3beta and exhibits high selectivity over a panel of other kinases. |
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| ln Vitro |
SAR502250 (0.01-1 μM; 36 h) attenuates the Aβ25-35-induced cell death in rat embryonic hippocampus neurons[2].
SAR502250 (0.01-1 microM; 36 h) attenuates Abeta25-35-induced cell death in rat embryonic hippocampal neurons, demonstrating neuroprotective activity. At concentrations above 1 microM, it effectively inhibits GSK-3 activity in cellular assays, reducing tau protein phosphorylation and enhancing neuronal survival under stress conditions. |
| ln Vivo |
In transgenic mice expressing P301L tau, SAR502250 (1–100 mg/kg; a single dose) attenuates tau hyperphosphorylation in the cortex and spinal cord[2]. Following Aβ25-35 infusion, SAR502250 (10–30 mg/kg; po once daily for 7 weeks) ameliorates the cognitive deficit in transgenic APP(SW)/Tau(VLW) mice[2]. In the inter-response time (IRT) bin (49-96 s), SAR502250 (10-30 mg/kg; one po) considerably raises the percentage of lever presses together with a notable rise in the percentage of reinforced responses[2]. SAR502250 (30 mg/kg; intraperitoneally once daily for 28 days) improves the physical state of the mice's coat that is deteriorated due to prolonged stress[2]. SAR502250 (10–60 mg/kg; one po) reduces the hyperactivity that stimulants cause in mice[2].
SAR502250 displays antidepressant-like activity and neuroprotective activity. In transgenic mice expressing P301L tau, SAR502250 (1-100 mg/kg; single oral dose) attenuates tau hyperphosphorylation in the cortex and spinal cord. In APP(SW)/Tau(VLW) mice, SAR502250 (10-30 mg/kg; p.o. once daily for 7 weeks) improves cognitive deficits. At 30 mg/kg (i.p.; 28 days), it ameliorates chronic stress-induced degradation of coat physical state in mice. |
| Enzyme Assay |
Cell-free GSK-3beta activity assays are performed using recombinant human GSK-3beta enzyme. The enzyme is incubated with a specific peptide substrate (derived from glycogen synthase) and [gamma-33P]-ATP or a luminescent ADP detection system in the presence of increasing concentrations of SAR502250 (0.001-10,000 nM) in assay buffer (50 mM HEPES, pH 7.4, 10 mM MgCl2). IC50 is determined by nonlinear regression. SAR502250 (12 nM; competitive with ATP) competes with ATP binding at the active site.
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| Cell Assay |
Rat embryonic hippocampal neurons are cultured and exposed to Abeta25-35 (neurotoxic peptide) for 36 hours to induce cell death. SAR502250 (0.01-1 microM) is added to the culture medium 1-2 hours before Abeta exposure. Cell viability is assessed by MTT or LDH release assays. Neurite outgrowth and synaptic integrity are evaluated by immunocytochemistry using antibodies against MAP2, synaptophysin, or tau phosphorylated at AD-relevant epitopes (e.g., AT8, PHF-1).
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| Animal Protocol |
Animal/Disease Models: Female P301L human tau transgenic mice (three-month-old; 32 g )[2]
Doses: 1, 3, 10, 30, 100 mg/kg Route of Administration: A single po Experimental Results: Attenuated dose-dependently tau phosphorylation in the cortex and spinal cord, with ED50s of 12.5 and 11.5 mg/kg, respectively. Transgenic mouse models: Tg2576 (APP) and P301L tau mice are used. SAR502250 is formulated in 0.5% methylcellulose (0.5% MC) or suitable vehicle. Dosing: once daily by oral gavage (10-30 mg/kg) for 4-7 weeks. Cognitive function is assessed by Morris water maze and novel object recognition. At study termination, brains are collected for biochemical analysis (tau phosphorylation by Western blot, amyloid-beta levels by ELISA) and immunohistochemistry (neuronal cell counts, glial activation). Chronic stress model: mice are subjected to restraint stress for 28 days with concurrent SAR502250 (30 mg/kg, i.p.). |
| ADME/Pharmacokinetics |
Oral bioavailability is good; SAR502250 is orally active and brain-penetrant (BBB-permeable). The molecular weight is 367.38 (C19H18FN5O2). Purity ≥99.0%. DMSO solubility: 90 mg/mL (ultrasonic). Storage: powder at -20degC for 3 years, in solvent at -80degC for 6 months. The compound is ATP-competitive, so its PK profile is typical for small-molecule kinase inhibitors with moderate half-life (t1/2) in rodents (likely 2-6 hours).
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for SAR502250 in the literature. In published in vivo studies at doses up to 100 mg/kg (single dose) or 30 mg/kg (repeated dosing for 7 weeks), no overt signs of toxicity (behavioral changes, weight loss, mortality) were reported. Standard toxicological assessments (hERG, Ames, repeat-dose toxicity in rats/dogs) would be required for clinical development. No FDA approval.
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| References |
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| Additional Infomation |
Other information: SAR502250 is a research compound (CAS 503860-57-9) not FDA-approved. It has been evaluated in preclinical Alzheimer‘s disease models and shows therapeutic potential due to its ability to reduce tau hyperphosphorylation, improve cognitive deficits, and provide neuroprotection. It also displays antidepressant-like activity, suggesting utility for neuropsychiatric symptoms associated with AD. Synonym: SAR502250.
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| Molecular Formula |
C19H18FN5O2
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|---|---|
| Molecular Weight |
367.38
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| Exact Mass |
367.144
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| CAS # |
503860-57-9
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| PubChem CID |
56589672
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| Appearance |
White to off-white solid powder
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| LogP |
2.019
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
617
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN1C(=O)C=C(N=C1N2CCO[C@H](C2)C3=CC=C(C=C3)F)C4=NC=NC=C4
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| InChi Key |
NKUNFNVAHJNALA-QGZVFWFLSA-N
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| InChi Code |
InChI=1S/C19H18FN5O2/c1-24-18(26)10-16(15-6-7-21-12-22-15)23-19(24)25-8-9-27-17(11-25)13-2-4-14(20)5-3-13/h2-7,10,12,17H,8-9,11H2,1H3/t17-/m1/s1
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| Chemical Name |
2-[(2S)-2-(4-fluorophenyl)morpholin-4-yl]-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one
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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: 100 mg/mL (272.20 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.80 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 (6.80 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 (6.80 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 | 2.7220 mL | 13.6099 mL | 27.2198 mL | |
| 5 mM | 0.5444 mL | 2.7220 mL | 5.4440 mL | |
| 10 mM | 0.2722 mL | 1.3610 mL | 2.7220 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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