| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
CPPHA targets metabotropic glutamate receptors, specifically mGluR5 and mGluR1. As a positive allosteric modulator (PAM), it binds to a site distinct from the orthosteric (glutamate) binding site. This binding enhances the receptor's response to glutamate, potentiating its signaling without directly activating the receptor itself. This mechanism offers a way to modulate glutamatergic signaling with greater spatial and temporal precision than orthosteric agonists.
|
|---|---|
| ln Vitro |
CPPHA alone has no agonist action [1]. CPPHA promotes a concentration-dependent increase of the responsiveness of human mGluR5 CHO cells to agonists [1]. CPPHA can boost the threshold response to glutamate in fluorescent Ca2+ assays by 7 to 8 times, with EC50 values in the range of 400 to 800 nM [1]. CPPHA (20 μM; 15 min) improves the reaction to subthreshold doses of DHPG on ERK and cyclic AMP response element binding protein (CREB) activity, as well as NMDA receptor subunit NR1 phosphorylation in cortical and hippocampal slices [3] .
In vitro, CPPHA acts as a selective PAM of mGluR5 and mGluR1. In recombinant CHO cells expressing human or rat mGluR5, it potentiates the response to glutamate, quisqualate, and DHPG by 4- to 7-fold. This means that in the presence of CPPHA, a lower concentration of the agonist is required to achieve the same level of receptor activation. This activity is measured using functional assays that detect receptor activation, such as calcium flux or IP3 accumulation. |
| ln Vivo |
In vivo, CPPHA is used as a research tool to study the function of mGluR5 and mGluR1 in the central nervous system. By potentiating the effects of glutamate, it can be used to probe the role of these receptors in various neurological and psychiatric conditions, including anxiety, depression, schizophrenia, and pain. Its effects are studied in animal models of these disorders to understand the therapeutic potential of mGluR PAMs.
|
| Enzyme Assay |
In vitro non-cell enzyme/receptor binding assays for CPPHA are not typical for allosteric modulators. Instead, its activity is assessed in functional assays using membrane preparations or whole cells. Radioligand binding studies can be used to confirm that it binds to a site distinct from the orthosteric site. However, the primary assay is a functional one that measures the potentiation of the receptor's response to an agonist.
|
| Cell Assay |
Western blot analysis [3]
Cell Types: Rat hippocampal cells Tested Concentrations: 20 μM Incubation Duration: 15 minutes Experimental Results: Enhanced DHPG (20 μM)-induced increase in ERK and CREB phosphorylation, approaching levels observed with 100 μM DHPG alone . In vitro cell-based assays for CPPHA use cell lines (e.g., recombinant CHO cells) that express mGluR5 or mGluR1. Cells are loaded with a calcium-sensitive dye, and the intracellular calcium flux is measured in response to a sub-maximal concentration of glutamate in the presence and absence of CPPHA. The compound's ability to potentiate the calcium response is quantified. This is the standard assay for measuring the activity of mGluR PAMs. |
| Animal Protocol |
In vivo animal studies for CPPHA would involve administering the compound to animal models of CNS disorders. Behavioral tests are then performed to assess its effects on various parameters, such as anxiety-like behavior, depressive-like behavior, cognitive function, or nociception. These studies help to determine the potential therapeutic applications of mGluR5/mGluR1 PAMs. CPPHA has a molecular weight of 406.82 g/mol and a molecular formula of C₂₂H₁₅ClN₂O₄. It is a solid with a purity of ≥98%. It is soluble in DMSO (>20 mg/mL). It should be stored desiccated at -20°C. As a small molecule, it is expected to be orally bioavailable and to cross the blood-brain barrier.
|
| ADME/Pharmacokinetics |
The toxicity profile of CPPHA is not extensively detailed in the provided search results. As a research compound, it is considered to have a manageable safety profile for laboratory use, but comprehensive toxicological data are not publicly available. It is classified with a GHS signal word of "Warning" and hazard statement H410 (Very toxic to aquatic life with long lasting effects). It is not intended for human therapeutic use without further development.
|
| Toxicity/Toxicokinetics |
CPPHA is a selective positive allosteric modulator (PAM) of the metabotropic glutamate receptors mGluR5 and mGluR1. It is used as a research tool to study the role of these receptors in the central nervous system and to develop potential therapeutics for neurological and psychiatric disorders. It is also known as N-{4-chloro-2-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide. It is not approved for clinical use.
|
| References |
|
| Molecular Formula |
C22H15N2O4CL
|
|---|---|
| Molecular Weight |
406.8185
|
| Exact Mass |
406.072
|
| CAS # |
693288-97-0
|
| PubChem CID |
9931205
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.506g/cm3
|
| Boiling Point |
539.7ºC at 760 mmHg
|
| Flash Point |
280.201ºC
|
| Index of Refraction |
1.733
|
| LogP |
4.105
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
29
|
| Complexity |
633
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
UFOUABRZSDGGAZ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H15ClN2O4/c23-14-9-10-18(24-20(27)17-7-3-4-8-19(17)26)13(11-14)12-25-21(28)15-5-1-2-6-16(15)22(25)29/h1-11,26H,12H2,(H,24,27)
|
| Chemical Name |
N-[4-chloro-2-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]-2-hydroxybenzamide
|
| 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 (~245.81 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.15 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 | 2.4581 mL | 12.2904 mL | 24.5809 mL | |
| 5 mM | 0.4916 mL | 2.4581 mL | 4.9162 mL | |
| 10 mM | 0.2458 mL | 1.2290 mL | 2.4581 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
