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MedKoo Cat#: 522386 | Name: ADX-47273
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

ADX-47273 is a potent and selective mGluR5 receptor PAM (positive allosteric modulator), EC50 = 0.17 μm, with no effect on other mGluR subtypes. 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. 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.

Chemical Structure

ADX-47273
CAS#851881-60-2

Theoretical Analysis

MedKoo Cat#: 522386

Name: ADX-47273

CAS#: 851881-60-2

Chemical Formula: C20H17F2N3O2

Exact Mass: 369.1289

Molecular Weight: 369.37

Elemental Analysis: C, 65.03; H, 4.64; F, 10.29; N, 11.38; O, 8.66

Price and Availability

Size Price Availability Quantity
25mg USD 250.00 2 Weeks
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
200mg USD 1,250.00 2 Weeks
500mg USD 2,650.00 2 Weeks
1g USD 3,850.00 2 Weeks
2g USD 6,250.00 2 Weeks
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No Data
Synonym
ADX-47273; ADX 47273; ADX47273.
IUPAC/Chemical Name
(S)-(4-fluorophenyl)(3-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)methanone
InChi Key
VXQCCZHCFBHTTD-HNNXBMFYSA-N
InChi Code
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
SMILES Code
O=C(C1=CC=C(F)C=C1)N2C[C@@H](C3=NC(C4=CC=C(F)C=C4)=NO3)CCC2
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
ADX-47273 is a brain-penetrant mGluR5 positive allosteric modulator (PAM), with an EC50 of 0.17 μM for potentiation of glutamate (50 nM) response.
In vitro activity:
ADX47273 caused a concentration-dependent increase in the response to 50 nM glutamate in HEK 293 cells expressing rat mGlu5 without eliciting a response by itself. The maximal increase in the response was approximately 9-fold, with an EC50 value for potentiation of 0.17 ± 0.03 μM (n = 8) (Fig. 1A). In primary astrocyte cultures, ADX47273 caused a concentration-dependent increase in the response to 300 nM glutamate, with an EC50 value of 0.23 ± 0.07 μM (n = 12) (Fig. 1B). Increasing concentrations of ADX47273 caused a parallel, leftward shift of the glutamate concentration response curve. In the presence of 0.1 or 1 μM ADX47273, the EC50 for glutamate decreased 4- and 9-fold, respectively, in HEK 293 cells expressing rat mGlu5 (Fig. 2A). Similarly in astrocytes, in the presence of 1 or 3 μM ADX47273, the EC50 for glutamate decreased 4- and 9-fold, respectively (Fig. 2B). The functional cross-selectivity of ADX47273 was evaluated in rat mGlu1, human mGlu2 (group II receptor), and mGlu4 (group III receptor) receptor cell lines. No agonist, antagonist, or allosteric responses were observed with ADX47273 (up to 10 μM) in any of the cell lines (data not shown). Reference: J Pharmacol Exp Ther. 2008 Dec;327(3):827-39. https://jpet.aspetjournals.org/content/327/3/827.long
In vivo activity:
In the ethanol-withdrawal group, post hoc (Bonferroni) test also revealed a significant increase in the primary latency and the number of primary errors committed in the 2nd (P < 0.01) and 3rd day (P < 0.01) trials in reaching the target hole. However, pretreatment with ADX-47273 (30 mg/kg, i.p.) significantly prevented the reversal learning impairment induced by ethanol withdrawal. Furthermore, ADX-47273 administration to the ethanol-withdrawn rats significantly decreased the primary latency and the number of committed primary errors on the 2nd (P < 0.01) and 3rd day (P < 0.01) trials. Reference: Behav Brain Res. 2018 Feb 15;338:9-16. https://pubmed.ncbi.nlm.nih.gov/29030082/
Solvent mg/mL mM comments
Solubility
DMSO 45.0 121.83
DMSO:PBS (pH 7.2) (1:3) 0.3 0.68
DMF 2.0 5.41
Ethanol 16.0 43.32
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 369.37 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
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 procognitive activities. J Pharmacol Exp Ther. 2008 Dec;327(3):827-39. doi: 10.1124/jpet.108.136580. Epub 2008 Aug 27. PMID: 18753411. 2. Marszalek-Grabska M, Gibula-Bruzda E, Bodzon-Kulakowska A, Suder P, Gawel K, Talarek S, Listos J, Kedzierska E, Danysz W, Kotlinska JH. ADX-47273, a mGlu5 receptor positive allosteric modulator, attenuates deficits in cognitive flexibility induced by withdrawal from 'binge-like' ethanol exposure in rats. Behav Brain Res. 2018 Feb 15;338:9-16. doi: 10.1016/j.bbr.2017.10.007. Epub 2017 Oct 10. PMID: 29030082. 3. Bikbaev A, Manahan-Vaughan D. Metabotropic glutamate receptor, mGlu5, regulates hippocampal synaptic plasticity and is required for tetanisation-triggered changes in theta and gamma oscillations. Neuropharmacology. 2017 Mar 15;115:20-29. doi: 10.1016/j.neuropharm.2016.06.004. Epub 2016 Jul 6. PMID: 27395786.
In vitro protocol:
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 procognitive activities. J Pharmacol Exp Ther. 2008 Dec;327(3):827-39. doi: 10.1124/jpet.108.136580. Epub 2008 Aug 27. PMID: 18753411.
In vivo protocol:
1. Marszalek-Grabska M, Gibula-Bruzda E, Bodzon-Kulakowska A, Suder P, Gawel K, Talarek S, Listos J, Kedzierska E, Danysz W, Kotlinska JH. ADX-47273, a mGlu5 receptor positive allosteric modulator, attenuates deficits in cognitive flexibility induced by withdrawal from 'binge-like' ethanol exposure in rats. Behav Brain Res. 2018 Feb 15;338:9-16. doi: 10.1016/j.bbr.2017.10.007. Epub 2017 Oct 10. PMID: 29030082. 2. Bikbaev A, Manahan-Vaughan D. Metabotropic glutamate receptor, mGlu5, regulates hippocampal synaptic plasticity and is required for tetanisation-triggered changes in theta and gamma oscillations. Neuropharmacology. 2017 Mar 15;115:20-29. doi: 10.1016/j.neuropharm.2016.06.004. Epub 2016 Jul 6. PMID: 27395786.
1: Xu J, Zhu Y, Kraniotis S, He Q, Marshall JJ, Nomura T, Stauffer SR, Lindsley CW, Conn PJ, Contractor A. Potentiating mGluR5 function with a positive allosteric modulator enhances adaptive learning. Learn Mem. 2013 Jul 18;20(8):438-45. doi: 10.1101/lm.031666.113. PubMed PMID: 23869026; PubMed Central PMCID: PMC3718201. 2: Kjaerby C, Bundgaard C, Fejgin K, Kristiansen U, Dalby NO. Repeated potentiation of the metabotropic glutamate receptor 5 and the alpha 7 nicotinic acetylcholine receptor modulates behavioural and GABAergic deficits induced by early postnatal phencyclidine (PCP) treatment. Neuropharmacology. 2013 Sep;72:157-68. doi: 10.1016/j.neuropharm.2013.04.041. Epub 2013 May 2. PubMed PMID: 23643744. 3: Clifton NE, Morisot N, Girardon S, Millan MJ, Loiseau F. Enhancement of social novelty discrimination by positive allosteric modulators at metabotropic glutamate 5 receptors: adolescent administration prevents adult-onset deficits induced by neonatal treatment with phencyclidine. Psychopharmacology (Berl). 2013 Feb;225(3):579-94. doi: 10.1007/s00213-012-2845-3. Epub 2012 Sep 16. PubMed PMID: 22983144. 4: Stauffer SR. Progress toward positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5). ACS Chem Neurosci. 2011 Aug 17;2(8):450-70. doi: 10.1021/cn2000519. Epub 2011 Jun 27. Review. PubMed PMID: 22860171; PubMed Central PMCID: PMC3369763. 5: Kroker KS, Rast G, Rosenbrock H. Differential effect of the mGlu5 receptor positive allosteric modulator ADX-47273 on early and late hippocampal LTP. Neuropharmacology. 2011 Sep;61(4):707-14. doi: 10.1016/j.neuropharm.2011.05.014. Epub 2011 May 27. PubMed PMID: 21640734. 6: Lamb JP, Engers DW, Niswender CM, Rodriguez AL, Venable DF, Conn PJ, Lindsley CW. 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. Bioorg Med Chem Lett. 2011 May 1;21(9):2711-4. doi: 10.1016/j.bmcl.2010.11.119. Epub 2010 Dec 3. PubMed PMID: 21183344; PubMed Central PMCID: PMC3179182. 7: Rosenbrock H, Kramer G, Hobson S, Koros E, Grundl M, Grauert M, Reymann KG, Schröder UH. Functional interaction of metabotropic glutamate receptor 5 and NMDA-receptor by a metabotropic glutamate receptor 5 positive allosteric modulator. Eur J Pharmacol. 2010 Aug 10;639(1-3):40-6. doi: 10.1016/j.ejphar.2010.02.057. Epub 2010 Apr 2. PubMed PMID: 20371241. 8: Schlumberger C, Pietraszek M, Gravius A, Danysz W. Effects of a positive allosteric modulator of mGluR5 ADX47273 on conditioned avoidance response and PCP-induced hyperlocomotion in the rat as models for schizophrenia. Pharmacol Biochem Behav. 2010 Mar;95(1):23-30. doi: 10.1016/j.pbb.2009.12.002. Epub 2009 Dec 5. PubMed PMID: 19995568. 9: Schlumberger C, Pietraszek M, Gravius A, Klein KU, Greco S, Morè L, Danysz W. Comparison of the mGlu(5) receptor positive allosteric modulator ADX47273 and the mGlu(2/3) receptor agonist LY354740 in tests for antipsychotic-like activity. Eur J Pharmacol. 2009 Nov 25;623(1-3):73-83. doi: 10.1016/j.ejphar.2009.09.006. Epub 2009 Sep 16. PubMed PMID: 19765575. 10: Bradley SJ, Watson JM, Challiss RA. Effects of positive allosteric modulators on single-cell oscillatory Ca2+ signaling initiated by the type 5 metabotropic glutamate receptor. Mol Pharmacol. 2009 Dec;76(6):1302-13. doi: 10.1124/mol.109.059170. Epub 2009 Sep 8. PubMed PMID: 19737913; PubMed Central PMCID: PMC2784724. 11: Engers DW, Rodriguez AL, Williams R, Hammond AS, Venable D, Oluwatola O, Sulikowski GA, Conn PJ, Lindsley CW. Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273. ChemMedChem. 2009 Apr;4(4):505-11. doi: 10.1002/cmdc.200800357. PubMed PMID: 19197923; PubMed Central PMCID: PMC2865690. 12: 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 procognitive activities. J Pharmacol Exp Ther. 2008 Dec;327(3):827-39. doi: 10.1124/jpet.108.136580. Epub 2008 Aug 27. PubMed PMID: 18753411. 13: de Paulis T, Hemstapat K, Chen Y, Zhang Y, Saleh S, Alagille D, Baldwin RM, Tamagnan GD, Conn PJ. Substituent effects of N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides on positive allosteric modulation of the metabotropic glutamate-5 receptor in rat cortical astrocytes. J Med Chem. 2006 Jun 1;49(11):3332-44. PubMed PMID: 16722652.