CPPHAMGluR5 receptor allosteric modulator CAS# 693288-97-0 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 693288-97-0 | SDF | Download SDF |
PubChem ID | 9931205 | Appearance | Powder |
Formula | C22H15ClN2O4 | M.Wt | 406.82 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : ≥ 58 mg/mL (142.57 mM) *"≥" means soluble, but saturation unknown. | ||
Chemical Name | N-[4-chloro-2-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]-2-hydroxybenzamide | ||
SMILES | C1=CC=C2C(=C1)C(=O)N(C2=O)CC3=C(C=CC(=C3)Cl)NC(=O)C4=CC=CC=C4O | ||
Standard InChIKey | UFOUABRZSDGGAZ-UHFFFAOYSA-N | ||
Standard InChI | 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) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Positive allosteric modulator at mGlu1 and mGlu5; thought to act at a novel allosteric site. Potentiates mGlu5 responses by a mechanism distinct from that of VU 29. |
CPPHA Dilution Calculator
CPPHA Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.4581 mL | 12.2904 mL | 24.5809 mL | 49.1618 mL | 61.4522 mL |
5 mM | 0.4916 mL | 2.4581 mL | 4.9162 mL | 9.8324 mL | 12.2904 mL |
10 mM | 0.2458 mL | 1.229 mL | 2.4581 mL | 4.9162 mL | 6.1452 mL |
50 mM | 0.0492 mL | 0.2458 mL | 0.4916 mL | 0.9832 mL | 1.229 mL |
100 mM | 0.0246 mL | 0.1229 mL | 0.2458 mL | 0.4916 mL | 0.6145 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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Description: IC50 Value: N/A CPPHA is a selective positive allosteric modulator of mGluR5 receptor. It has no agonist activity alone, but reduces threshold response and shifts dose-response curves to glutamate, quisqualate, and DHPG by 4- to 7-fold to the left in recombinant CHO cells expressing human or rat mGluR5. in vitro: The selective mGlu5 receptor positive allosteric modulator, N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2yl)-methyl]phenyl}-2-hydrobenzamide (CPPHA) potentiated the response to a subthreshold concentration of 3,5-dihydroxy-phenylglycine (DHPG) on extracellular signal-regulated protein kinase (ERK) and cyclic-AMP responsive element-binding protein (CREB) activity, as well as N-methyl d-aspartate (NMDA) receptor subunit NR1 phosphorylation in cortical and hippocampal slices [1]. CPPHA potentiated threshold responses to glutamate in fluorometric Ca(2+) assays 7- to 8-fold with EC(50) values in the 400 to 800 nM range, and at 10 microM shifted mGluR5 agonist concentration-response curves to glutamate, quisqualate, and (R,S)-3,5-dihydroxyphenylglycine (DHPG) 4- to 7-fold to the left. CPPHA (10 microM) potentiated NMDA receptor currents in hippocampal slices induced by threshold levels of DHPG, whereas having no effect on these currents by itself. Similarly, 10 microM CPPHA also potentiated mGluR5-mediated DHPG-induced depolarization of rat subthalamic nucleus neurons [2]. CPPHA induced an increase in basal mGluR5-mediated ERK1/2 phosphorylation and potentiated the effect of low concentrations of agonists. In contrast, CPPHA significantly decreased ERK1/2 phosphorylation induced by high concentrations of agonists [3]. in vivo: N/A Toxicity: N/A Clinical trial: N/A
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Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA.[Pubmed:17210250]
Bioorg Med Chem Lett. 2007 Mar 1;17(5):1386-91.
This Letter describes, for the first time, the synthesis and SAR, developed through an iterative analog library approach, that led to the discovery of the positive allosteric modulator (PAM) of the metabotropic glutamate receptor mGluR5 CPPHA. Binding to a unique allosteric binding site distinct from other mGluR5 PAMs, CPPHA has been the focus of numerous pharmacology studies by several laboratories.
N-{4-Chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybe nzamide (CPPHA) acts through a novel site as a positive allosteric modulator of group 1 metabotropic glutamate receptors.[Pubmed:18056795]
Mol Pharmacol. 2008 Mar;73(3):909-18.
Recent studies suggest that a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor (mGluRs), mGluR5, termed 4-nitro-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (VU-29), potentiates mGluR5 responses by actions at a site that is overlapping with the binding site of 2-methyl-6-(phenylethynyl)pyridine (MPEP), a previously identified negative allosteric modulator of this receptor. It is interesting that a structurally distinct PAM, N-{4-Chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybe nzamide (CPPHA), does not to bind to the MPEP site. We now report that CPPHA potentiates mGluR5 responses by a mechanism that is distinct from that of VU-29. VU-29- and CPPHA-induced potentiation of mGluR5 responses are blocked by a neutral ligand at the MPEP allosteric site termed 5-methyl-2-(phenylethynyl)pyridine (5MPEP). However, increasing concentrations of 5MPEP induce parallel rightward shifts in the VU-29 concentration-response curve, whereas 5MPEP inhibits CPPHA potentiation in a noncompetitive manner. Consistent with this, a mutation (A809V/mGluR5) that reduces binding of ligands to the MPEP site eliminates the effect of VU-29 but has no effect on the response to CPPHA. On the other hand, a mutation (F585I/mGluRs) that eliminates the effect of CPPHA does not alter the response to VU-29. CPPHA is also a PAM at mGluR1. It is interesting that the corresponding mutation of F585I/mGluR5 in mGluR1 (F599I/mGluR1) eliminates CPPHA's effect without altering the potentiation of a known PAM of mGluR1, (S)-2-(4-fluorophenyl)-1-(toluene-4-sulfonyl)pyrrolidine (Ro 67-7476). Likewise, another mutation (V757L/mGluR1) that abolishes potentiation of Ro 67-7476 has no effect on CPPHA. Finally, CPPHA does not displace binding of a radioligand for the mGluR1 allosteric antagonist characterized previously. Together, these data suggest that CPPHA acts at a novel allosteric site on both mGluR1 and -5 to potentiate responses to activation of these receptors.