| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
AMPA receptor (associated with TARP γ-8) (GluA1/γ-8 pIC₅₀ = 9.7) [1]
|
|---|---|
| ln Vitro |
AMPA Receptor Modulator-1 includes benzimidazolone-based compound 3 (JNJ-55511118) and oxindole-based compound 18, which are negative modulators of AMPA receptors (AMPARs) associated with TARP γ-8. [1]
Compound 18 (a 5-aryl oxindole derivative) exhibits high potency against GluA1/γ-8 with a pIC₅₀ value of 9.7. [1] The benzimidazolone core of compound 3 was replaced with an oxindole moiety, which mitigated the formation of reactive metabolites. [1] Compound 3 was optimized from high-throughput screen (HTS) lead 4 for improved potency and brain penetration. [1] |
| ln Vivo |
Following oral dosing in rats, compound 18 (a member of AMPA Receptor Modulator-1) demonstrated robust target engagement in the hippocampus as evaluated by ex vivo autoradiography, with an ED₅₀ of 0.6 mg/kg and a plasma EC₅₀ of 9 ng/mL. [1]
|
| Animal Protocol |
Rats were administered compound 18 (a member of AMPA Receptor Modulator-1) via oral gavage. [1]
At the Tₘₐₓ of each compound, ex vivo autoradiography was performed to assess receptor occupancy in the rat hippocampus, using [³H]-12 as the radiotracer. [1] The experiment was conducted with 3 rats per dose group, and the data were presented as mean ± SEM. [1] |
| ADME/Pharmacokinetics |
Compound 3 (a member of the AMPA receptor modulator-1 family) underwent cross-species hepatocyte metabolic analysis (data shown in Figure 3). [1]
After oral administration of compound 18 to rats, plasma EC₅₀ was 9 ng/mL, and it showed brain permeability, exhibiting binding to hippocampal targets. [1] |
| Toxicity/Toxicokinetics |
The substitution of the benzimidazolone core in compound 3 with an indoleone skeleton (resulting in compound 18, a member of the AMPA receptor modulator-1 family) reduces the production of the active metabolite, which may be related to a reduction in potential toxicological risks. [1]
|
| References | |
| Additional Infomation |
Glutamate mediates rapid excitatory neurotransmission via ionotropic AMPA receptors (AMPARs), and transmembrane AMPA regulatory protein (TARP) can enhance the transport and gating properties of AMPAs; TARP γ-8 is the major TARP expressed in the hippocampus. [1]
AMPA receptor modulator-1, composed of 5-arylbenzimidazolone and indoleone derivatives, was developed as a selective negative modulator of TARP γ-8-related AMPAs. [1] Compound 3 (JNJ-55511118) is a benzimidazolone-based modulator optimized from high-throughput screening of lead compound 4 to improve its potency and brain penetration. [1] Compound 18 is a 5-arylindoleone-based modulator identified through a core substitution strategy to address the active metabolite problem. [1] |
| Molecular Formula |
C16H11CLF3NO2
|
|---|---|
| Molecular Weight |
341.71
|
| Exact Mass |
341.043
|
| CAS # |
2036074-41-4
|
| PubChem CID |
122655505
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.6
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
23
|
| Complexity |
459
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
AYAICAKEBFTALD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H11ClF3NO2/c1-8-5-9(6-10-7-13(22)21-15(8)10)14-11(17)3-2-4-12(14)23-16(18,19)20/h2-6H,7H2,1H3,(H,21,22)
|
| Chemical Name |
5-[2-chloro-6-(trifluoromethoxy)phenyl]-7-methyl-1,3-dihydroindol-2-one
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.9265 mL | 14.6323 mL | 29.2646 mL | |
| 5 mM | 0.5853 mL | 2.9265 mL | 5.8529 mL | |
| 10 mM | 0.2926 mL | 1.4632 mL | 2.9265 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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