| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
AZ12216052 targets mGluR8, a presynaptic group III metabotropic glutamate receptor involved in the regulation of neurotransmitter release. As a positive allosteric modulator, it binds to an allosteric site on the receptor and enhances the receptor's response to the endogenous agonist glutamate. This modulation helps mGluR8 regulate signal input to retinal ganglion cells.
|
|---|---|
| ln Vitro |
Retinal ganglion cells' synaptic input is regulated by mGluR8 [1]. Depending on the strength of light stimulation, AZ 12216052 (10 μM) increases the peak excitatory currents of switching currents in switch ganglion cells [1]. In human neuroblastoma SH-SY5Y cells, AZ 12216052 (0.01-1 μM; 24-48 hours) partially decreased Dox-induced damage and shown effects on cell differentiation [2]. In UN-SH-SY5Y cells, AZ 12216052 promotes proliferation and reduces the toxicity caused by doxorubicin (Dox) and staurosporine (St) [2]. The glutamate activity of human mGluR8b receptors expressed in GHEK cells is enhanced by AZ12216052 (10 μM) [3].
In vitro, AZ12216052 potentiates glutamate-induced [35S]GTPγS binding in GHEK cells expressing human mGluR8b with an EC50 of 1 μM. This demonstrates its activity as a positive allosteric modulator of mGluR8. The compound's ability to enhance mGluR8 signaling makes it a useful tool for studying glutamatergic circuit modulation. |
| ln Vivo |
Mice's anxiety levels are lowered by AZ 12216052 (10 mg/kg; intraperitoneal injection; two hours prior to testing) without altering their speed [3]. In mice lacking mGluR8, AZ12216052 (10 mg/kg; i.p.; single dose) shows lingering anxiolytic effects that might be related to mGluR4 because mGluR4 PAM (positive allosteric modulator) VU 0155041 similarly lowers the levels of anxiety in mice with wild-type [4].
In vivo, AZ12216052 exhibits anxiolytic effects in mouse models of anxiety. It is a positive allosteric modulator of mGluR8 that helps mGluR8 modulate signaling input to retinal ganglion cells. The compound's anxiolytic effects have been demonstrated in animal models, making it a valuable tool for studying the role of mGluR8 in anxiety and other CNS disorders. |
| Enzyme Assay |
The activity of AZ12216052 at mGluR8 can be assessed using cell-based functional assays. Cells expressing the human mGluR8b receptor are treated with varying concentrations of the compound in the presence of a submaximal concentration of glutamate. The potentiation of receptor signaling is measured using [35S]GTPγS binding or other downstream signaling assays. The EC50 for potentiation is determined from dose-response curves.
|
| Cell Assay |
Cell Viability Assay[2]
Cell Types: UN- and RA-SH-SY5Y Cell Tested Concentrations: 0.01-1 μM Incubation Duration: 48 hrs (hours) Experimental Results: Cell viability increased at 0.1 μM and protected undifferentiated neuroblastoma cells against Destructive effects of Iri or Cis. To evaluate the cellular effects of AZ12216052, cells expressing mGluR8 are treated with the compound, and the modulation of glutamate-induced signaling is measured. This can include the measurement of downstream second messengers such as cAMP or calcium. The compound's ability to enhance mGluR8-mediated inhibition of neurotransmitter release can also be assessed in neuronal cultures. |
| Animal Protocol |
Animal/Disease Models: WT and apolipoprotein E-deficient (Apoe−/−) mice (C57BL/6J, 2 months old) in the elevated zero maze [3]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; intraperitoneal (ip) injection. Single dose, 2 hrs (hrs (hours)) before testing Experimental Results: diminished anxiety measures in the elevated zero maze without affecting mice's speed. Reduce sound startle response. In vivo studies with AZ12216052 typically involve administration to rodents via oral or intraperitoneal routes. In models of anxiety, such as the elevated plus maze or light-dark box, the compound's anxiolytic effects are assessed. Other behavioral and physiological parameters can also be measured to characterize the compound's in vivo profile. |
| ADME/Pharmacokinetics |
AZ12216052 has a molecular formula of C19H22BrNOS and a molecular weight of 392.35. Its CAS number is 1290628-31-7. The compound is soluble in DMSO (39.23 mg/mL). It is a positive allosteric modulator of mGluR8.
|
| Toxicity/Toxicokinetics |
Specific toxicology data for AZ12216052 are not detailed in the available literature. However, its anxiolytic effects in mouse models suggest it is tolerated at effective doses. As with all research compounds, standard safety precautions should be taken during handling.
|
| References |
|
| Additional Infomation |
AZ12216052 is a positive allosteric modulator of mGluR8 used as a research tool to study glutamatergic signaling and CNS circuit modulation. It exhibits anxiolytic effects and is useful for studying the role of mGluR8 in anxiety and other psychiatric disorders. It is not a clinically approved drug.
|
| Molecular Formula |
C17H26BNO2SI
|
|---|---|
| Molecular Weight |
315.290345668793
|
| Exact Mass |
391.061
|
| CAS # |
1290628-31-7
|
| PubChem CID |
73755190
|
| Appearance |
White to off-white solid powder
|
| LogP |
5.907
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
23
|
| Complexity |
349
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
QKUYZJOTWYRWNF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H22BrNOS/c1-3-14(2)16-6-10-18(11-7-16)21-19(22)13-23-12-15-4-8-17(20)9-5-15/h4-11,14H,3,12-13H2,1-2H3,(H,21,22)
|
| Chemical Name |
2-[(4-bromophenyl)methylsulfanyl]-N-(4-butan-2-ylphenyl)acetamide
|
| 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 : ~100 mg/mL (~254.87 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.37 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1717 mL | 15.8584 mL | 31.7168 mL | |
| 5 mM | 0.6343 mL | 3.1717 mL | 6.3434 mL | |
| 10 mM | 0.3172 mL | 1.5858 mL | 3.1717 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
