ADX-47273mGluR5 receptor positive allosteric modulator, potent and selective CAS# 851881-60-2 |
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| Cas No. | 851881-60-2 | SDF | Download SDF |
| PubChem ID | 11383075 | Appearance | Powder |
| Formula | C20H17F2N3O2 | M.Wt | 369.36 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 31 mg/mL (83.93 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | (4-fluorophenyl)-[(3S)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone | ||
| SMILES | C1CC(CN(C1)C(=O)C2=CC=C(C=C2)F)C3=NC(=NO3)C4=CC=C(C=C4)F | ||
| Standard InChIKey | VXQCCZHCFBHTTD-HNNXBMFYSA-N | ||
| Standard InChI | InChI=1S/C20H17F2N3O2/c21-16-7-3-13(4-8-16)18-23-19(27-24-18)15-2-1-11-25(12-15)20(26)14-5-9-17(22)10-6-14/h3-10,15H,1-2,11-12H2/t15-/m0/s1 | ||
| 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 | ADX-47273 is a positive allosteric modulator selective for the metabotropic glutamate receptor subtype mGluR5(EC50=170 nM).
IC50 value: 170 nM(EC50) [1] [2]
Target: positive allosteric modulator (PAM) of mGluR5
in vitro: ADX-47273 increased (9-fold) the response to threshold concentration of glutamate (50 nM) in fluorometric Ca(2+) assays (EC(50) = 170 nM) in human embryonic kidney 293 cells expressing rat mGlu5. ADX47273 dose-dependently shifted mGlu5 receptor glutamate response curve to the left (9-fold at 1 microM) and competed for binding of [(3)H]2-methyl-6-(phenylethynyl)pyridine (K(i) = 4.3 microM), but not [(3)H]quisqualate [2].
in vivo: ADX47273 increased extracellular signal-regulated kinase and cAMP-responsive element-binding protein phosphorylation in hippocampus and prefrontal cortex, both of which are critical for glutamate-mediated signal transduction mechanisms. In models sensitive to antipsychotic drug treatment, ADX47273 reduced rat-conditioned avoidance responding [minimal effective dose (MED) = 30 mg/kg i.p.] and decreased mouse apomorphine-induced climbing (MED = 100 mg/kg i.p.), with little effect on stereotypy or catalepsy [2]. ADX47273 had no effect on single-session and multi-session extinction, but administration of ADX47273 after a single retrieval trial enhanced subsequent fear extinction learning [3]. References: | |||||
ADX-47273 Dilution Calculator
ADX-47273 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.7074 mL | 13.5369 mL | 27.0739 mL | 54.1477 mL | 67.6846 mL |
| 5 mM | 0.5415 mL | 2.7074 mL | 5.4148 mL | 10.8295 mL | 13.5369 mL |
| 10 mM | 0.2707 mL | 1.3537 mL | 2.7074 mL | 5.4148 mL | 6.7685 mL |
| 50 mM | 0.0541 mL | 0.2707 mL | 0.5415 mL | 1.083 mL | 1.3537 mL |
| 100 mM | 0.0271 mL | 0.1354 mL | 0.2707 mL | 0.5415 mL | 0.6768 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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ADX-47273 is a potent and selective mGluR5 receptor PAM (positive allosteric modulator), EC50 = 0.17 μm, with no effect on other mGluR subtypes. [1]
The mGluR (metabotropic glutamate receptor) is a group of G-protein coupled receptors and is active through an indirect metabotropic process. It plays a critical role in regulating synaptic plasticity and neural network activity.
In HEK-293 cell expressing rat mGlu5, ADX-showed 9-fold higher response (EC50 = 0.17 μm) to threshold concentration of glutamate (50 nM) in the fluorometric Ca2+ assays, it also shifted mGlu5 receptor glutamate response curve to the left. [1]
In vivo, ADX47273 increased ERK (extracellular signal-regulated kinase) and CREB (cAMP-responsive element-binding protein) phosphorylation in rat hippocampus and prefrontal cortex. In rat and mouse models that sensitive to antipsychotic treatment, ADX47273 decreased rat conditioned avoidance responding (minimal effective dose = 30 mg/kg i.p.) and reduced mouse ampomorphine-activated climbing (minimal effective dose = 100 mg/kg i.p.) [1]
Reference:
[1] Liu F, Grauer S, Kelley C, Navarra R, Graf R, Zhang G, Atkinson PJ, Popiolek M, Wantuch C, Khawaja X, Smith D, Olsen M, Kouranova E, Lai M, Pruthi F, Pulicicchio C, Day M, Gilbert A, Pausch MH, Brandon NJ, Beyer CE, Comery TA, Logue S, Rosenzweig-Lipson S, Marquis KL. ADX47273 [S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]-oxadiazol-5-yl]-piperidin-1-yl}-methanone]: a novel metabotropic glutamate receptor 5-selective positive allosteric modulator with preclinical antipsychotic-like and precognitive activities. J Pharmacol Exp Ther. 2008 Dec;327(3):827-39.
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Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273.[Pubmed:19197923]
ChemMedChem. 2009 Apr;4(4):505-11.
An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago-potentiator ADX-47273. This effort identified key substituents in the 3-position of oxadiazole that engendered either mGluR5 ago-potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.
Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists.[Pubmed:21183344]
Bioorg Med Chem Lett. 2011 May 1;21(9):2711-4.
This Letter describes a chemical lead optimization campaign directed at a weak mGlu(5) NAM discovered while developing SAR for the mGlu(5) PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu(5) NAMs, mGlu(5) PAMs as well as mGlu(5) partial antagonists.
Differential effect of the mGlu5 receptor positive allosteric modulator ADX-47273 on early and late hippocampal LTP.[Pubmed:21640734]
Neuropharmacology. 2011 Sep;61(4):707-14.
Conflicting findings are reported in the literature about the involvement of the mGlu5 receptor in hippocampal long-term potentiation (LTP), which might be a consequence of different sub-types of LTP induced by the investigators due to the specific experimental conditions used. A comparable controversy came up in the past concerning the influence of different experimental conditions on the involvement of L-type voltage dependent calcium channels (L-VDCCs) and NMDA receptors in hippocampal LTP. In this study, two stimulation protocols with otherwise identical conditions were used to probe modulatory effects of mGlu5 receptor activation in NMDA receptor and L-VDCCs dependent CA1 LTP: weak high frequency stimulation (20 stimuli at 100 Hz) to induce early LTP and repeated strong high frequency stimulation (3 times 100 stimuli at 100 Hz with 5 min interval) to induce late LTP, which - in contrast to early LTP - was shown to be protein-synthesis dependent. Using the NMDA receptor antagonist MK-801 and the L-type calcium channel blocker nifedipine, early LTP was shown to be dependent on NMDA receptors only, whereas late LTP was demonstrated to be dependent on NMDA receptors and L-VDCCs in about equal parts. Moreover, late LTP, but not early LTP, was increased by the mGlu5 receptor positive allosteric modulator ADX-47273, indicating that artificial augmentation of mGlu5 receptor activation by endogenous glutamate may boost the protein-synthesis dependent form of LTP but not the protein-synthesis independent form.
