| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg | ||
| Other Sizes |
| Targets |
BACE1 20 μM (IC50) AChE 1 μM (IC50) GSK-3β 15 μM (IC50)
|
|---|---|
| ln Vitro |
AChE/BACE1/GSK3β-IN-1 showed efficient inhibition for AChE, BACE1 and GSK3β with IC50 values of 1.0 μM, 20 μM and 15 μM, respectively[1]. AChE/BACE1/GSK3β-IN-1 can pass through BBB[1].
|
| ln Vivo |
In C57B6/J mice, oral AChE/BACE1/GSK3β-IN-1 (200 and 400 mg/kg, single) exhibits minimal acute toxicity and an excellent safety profile[1]. The PK profiles of AChE/BACE1/GSK3β-IN-1 (po, 100 mg/kg; iv, 10 mg/kg) are good[1]. In mice with Alzheimer's disease (AD) produced by Aβ, AChE/BACE1/GSK3β-IN-1 (gavage, 2.5 mg/kg, 5 mg/kg, and 10 mg/kg, for 7 consecutive days) can improve learning and memory impairment[1]. ADAM17 expression in the brain is inhibited by AChE/BACE1/GSK3β-IN-1, and the expressions of BACE1 and ADAM17 in AD animals are considerably reduced[1].
|
| Animal Protocol |
Animal/Disease Models: C57B6/J Mice[1]
Doses: 200 and 400 mg/kg Route of Administration: po (oral gavage) single Experimental Results: Increased slightly serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), but no significant difference. demonstrated no significant change in the content of blood urea nitrogen (BUN). Did not change Dramatically the morphology of liver and kidney tissue of mice. Animal/Disease Models: male SD (Sprague-Dawley) rats[1] Doses: 10 mg/kg and 100 mg/kg Route of Administration: oral and intravenous (iv) Experimental Results: parameters 100 mg/kg (po) 10 mg/kg(iv) Cmax(ng/mL) 167 ± 13 2796 ± 259 AUC0−t(ng/mL) 1010 ± 112 1031 ± 86 AUC0− ∞(ng/mL*h) 1635 ± 362 1047 ± 88 t1/2 (h) 20 ± 9 0.4 ± 0.04 Cl (L/h/kg) 63 ± 12 10 ± 1 MRT0−∞(h) 26 ± 11 0.3 ± 0 VZ(L/kg) 1730 ± 387 5 ± 1 Tmax(h) 1 0.08 F (%) 9.8. Animal/Disease Models: Aβ-induced AD mice[1] Doses: 2.5 mg/kg, 5 mg/kg and 10mg/ kg Route of Administration: gavage, for 7 days Experimental Results: diminished the escape latency of mice. Increased the number of crossing platforms in mice in a dose- |
| References |
[1]. Nan Wang, et al. Design, Synthesis, and Biological Evaluation of Notopterol Derivatives as Triple Inhibitors of AChE/BACE1/GSK3β for the Treatment of Alzheimer’s Disease. ACS Omega 2022, 7, 36, 32131–32152. Publication Date:August 30, 2022.
|
| Molecular Formula |
C26H27FN2O4
|
|---|---|
| Molecular Weight |
450.50
|
| CAS # |
2866066-81-9
|
| 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 | 2.2198 mL | 11.0988 mL | 22.1976 mL | |
| 5 mM | 0.4440 mL | 2.2198 mL | 4.4395 mL | |
| 10 mM | 0.2220 mL | 1.1099 mL | 2.2198 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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