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MedKoo Cat#: 319677 | Name: Mavoglurant
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Description:

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

Mavoglurant, aslo known as AFQ056, is a potent, selective, non-competitive and orally active mGluR5 antagonist, In vitro, mavoglurant had an IC50 of 30 nM in a functional assay with human mGluR5 and was selective over the other mGluR subtypes, iGluRs and a panel of 238 CNS relevant receptors, transporter or enzymes. In vivo, mavoglurant showed an improved pharmacokinetic profile in rat and efficacy in the stress-induced hyperthermia test in mice as compared to the prototypic mGluR5 antagonist MPEP.

Chemical Structure

Mavoglurant
Mavoglurant
CAS#543906-09-8

Theoretical Analysis

MedKoo Cat#: 319677

Name: Mavoglurant

CAS#: 543906-09-8

Chemical Formula: C19H23NO3

Exact Mass: 313.1678

Molecular Weight: 313.40

Elemental Analysis: C, 72.82; H, 7.40; N, 4.47; O, 15.32

Price and Availability

Size Price Availability Quantity
1mg USD 190.00 Ready to ship
5mg USD 550.00 Ready to ship
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Related CAS #
No Data
Synonym
AFQ056; AFQ-056; AFQ 056; Mavoglurant.
IUPAC/Chemical Name
methyl (3aR,4S,7aR)-4-hydroxy-4-(m-tolylethynyl)octahydro-1H-indole-1-carboxylate
InChi Key
ZFPZEYHRWGMJCV-ZHALLVOQSA-N
InChi Code
InChI=1S/C19H23NO3/c1-14-5-3-6-15(13-14)8-11-19(22)10-4-7-17-16(19)9-12-20(17)18(21)23-2/h3,5-6,13,16-17,22H,4,7,9-10,12H2,1-2H3/t16-,17-,19-/m1/s1
SMILES Code
O=C(N1CC[C@@]2([H])[C@@](C#CC3=CC=CC(C)=C3)(O)CCC[C@@]12[H])OC
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
Biological target:
Mavoglurant (AFQ056) is a potent, selective, non-competitive and orally active mGluR5 antagonist, with an IC50 of 30 nM.
In vitro activity:
To determine whether AFQ056 may have secondary effects on the methylation and transcription of FMR1, three FXS lymphoblastoid cell lines and one normal control male line were treated. A quantitative RT-PCR was performed to assess transcriptional reactivation of the FMR1 gene. No FMR1-mRNA increase was observed after treatment with AFQ056 in any of the four cell lines, with respect to the untreated controls. The partial decrease in FMR1 transcription observed in WT at 1 mM AFQ056 after 3 and 8 days of treatment (panel A) was due at least in part to cell mortality. AFQ056 treatment had no effect on methylation, leaving the promoter as methylated as in the untreated controls both WT and FXS (Figure 22). These results demonstrate that the AFQ056 effect on fully methylated FXS patients is not due to a secondary effect on DNA methylation and consequent transcriptional activation of FMR1. Reference: BMC Med Genet. 2012; 13: 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320553/
In vivo activity:
In this study, the activity of the metabotropic glutamate receptor-5 (mGluR5) was inhibited using AFQ056/Mavoglurant, a drug that is assumed to normalize excitatory/inhibitory neural signaling imbalances in FXS. Resting-state-fMRI (rs-fMRI) and diffusion-weighted imaging (DWI) were employed to test whether Mavoglurant re-established brain connectivity - at least partly - within some of the affected circuits in Fmr1-/y mice that are related to social behavior deficits. In line with previous findings, it was observed that Fmr1/y mice exhibited impaired social interaction, reduced connectivity in three main functional networks and altered network topology. At the group level, Mavoglurant did neither rescue abnormal social behavioral nor white matter abnormalities; however, for some, but not all of these circuits Mavoglurant had a genotype-specific effect of restoring functional connectivity. Analyses of network connectivity strength showed that chronic treatment with AFQ056/Mavoglurant was sufficient to restore the connectivity profile towards Fmr1+/y levels in temporal associative and somatosensory networks (Genotype × Treatment interaction, p-value = 0.009 and 0.001, respectively), but not in anterior-posterior cingulate network (p-value = 0.136).These results show that rs-fMRI connectivity is sufficiently sensitive to pick up system-level changes after the pharmacological inhibition of mGluR5 activity. Overall, the effects of Mavoglurant are confined to specific networks suggesting that behavioral benefits might be restricted to narrow functional domains. Reference: Neuroimage. 2019 May 1;191:392-402. https://pubmed.ncbi.nlm.nih.gov/30807820/
Solvent mg/mL mM
Solubility
DMSO 120.0 382.91
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 313.40 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. Tabolacci E, Pirozzi F, Gomez-Mancilla B, Gasparini F, Neri G. The mGluR5 antagonist AFQ056 does not affect methylation and transcription of the mutant FMR1 gene in vitro. BMC Med Genet. 2012 Mar 7;13:13. doi: 10.1186/1471-2350-13-13. PMID: 22397687; PMCID: PMC3320553. 2. Vranesic I, Ofner S, Flor PJ, Bilbe G, Bouhelal R, Enz A, Desrayaud S, McAllister K, Kuhn R, Gasparini F. AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: identification, SAR and pharmacological characterization. Bioorg Med Chem. 2014 Nov 1;22(21):5790-803. doi: 10.1016/j.bmc.2014.09.033. Epub 2014 Sep 20. PMID: 25316499. 3. Vranesic I, Ofner S, Flor PJ, Bilbe G, Bouhelal R, Enz A, Desrayaud S, McAllister K, Kuhn R, Gasparini F. AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: identification, SAR and pharmacological characterization. Bioorg Med Chem. 2014 Nov 1;22(21):5790-803. doi: 10.1016/j.bmc.2014.09.033. Epub 2014 Sep 20. PMID: 25316499. 3. Vranesic I, Ofner S, Flor PJ, Bilbe G, Bouhelal R, Enz A, Desrayaud S, McAllister K, Kuhn R, Gasparini F. AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: identification, SAR and pharmacological characterization. Bioorg Med Chem. 2014 Nov 1;22(21):5790-803. doi: 10.1016/j.bmc.2014.09.033. Epub 2014 Sep 20. PMID: 25316499. 3. Zerbi V, Markicevic M, Gasparini F, Schroeter A, Rudin M, Wenderoth N. Inhibiting mGluR5 activity by AFQ056/Mavoglurant rescues circuit-specific functional connectivity in Fmr1 knockout mice. Neuroimage. 2019 May 1;191:392-402. doi: 10.1016/j.neuroimage.2019.02.051. Epub 2019 Feb 23. PMID: 30807820.
In vitro protocol:
1. Tabolacci E, Pirozzi F, Gomez-Mancilla B, Gasparini F, Neri G. The mGluR5 antagonist AFQ056 does not affect methylation and transcription of the mutant FMR1 gene in vitro. BMC Med Genet. 2012 Mar 7;13:13. doi: 10.1186/1471-2350-13-13. PMID: 22397687; PMCID: PMC3320553. 2. Vranesic I, Ofner S, Flor PJ, Bilbe G, Bouhelal R, Enz A, Desrayaud S, McAllister K, Kuhn R, Gasparini F. AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: identification, SAR and pharmacological characterization. Bioorg Med Chem. 2014 Nov 1;22(21):5790-803. doi: 10.1016/j.bmc.2014.09.033. Epub 2014 Sep 20. PMID: 25316499.
In vivo protocol:
1. Vranesic I, Ofner S, Flor PJ, Bilbe G, Bouhelal R, Enz A, Desrayaud S, McAllister K, Kuhn R, Gasparini F. AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: identification, SAR and pharmacological characterization. Bioorg Med Chem. 2014 Nov 1;22(21):5790-803. doi: 10.1016/j.bmc.2014.09.033. Epub 2014 Sep 20. PMID: 25316499. 2. Zerbi V, Markicevic M, Gasparini F, Schroeter A, Rudin M, Wenderoth N. Inhibiting mGluR5 activity by AFQ056/Mavoglurant rescues circuit-specific functional connectivity in Fmr1 knockout mice. Neuroimage. 2019 May 1;191:392-402. doi: 10.1016/j.neuroimage.2019.02.051. Epub 2019 Feb 23. PMID: 30807820.
1: Negida A, Ghaith HS, Fala SY, Ahmed H, Bahbah EI, Ebada MA, Aziz MAE. Mavoglurant (AFQ056) for the treatment of levodopa-induced dyskinesia in patients with Parkinson's disease: a meta-analysis. Neurol Sci. 2021 Aug;42(8):3135-3143. doi: 10.1007/s10072-021-05319-7. Epub 2021 May 20. PMID: 34014397; PMCID: PMC8342336. 2: Streffer J, Treyer V, Buck A, Ametamey SM, Blagoev M, Maguire RP, Gautier A, Auberson YP, Schmidt ME, Vranesic IT, Gomez-Mancilla B, Gasparini F. Regional brain mGlu5 receptor occupancy following single oral doses of mavoglurant as measured by [11C]-ABP688 PET imaging in healthy volunteers. Neuroimage. 2021 Apr 15;230:117785. doi: 10.1016/j.neuroimage.2021.117785. Epub 2021 Feb 2. PMID: 33545349. 3: Zerbi V, Markicevic M, Gasparini F, Schroeter A, Rudin M, Wenderoth N. Inhibiting mGluR5 activity by AFQ056/Mavoglurant rescues circuit-specific functional connectivity in Fmr1 knockout mice. Neuroimage. 2019 May 1;191:392-402. doi: 10.1016/j.neuroimage.2019.02.051. Epub 2019 Feb 23. PMID: 30807820. 4: Hessl D, Harvey D, Sansone S, Crestodina C, Chin J, Joshi R, Hagerman RJ, Berry-Kravis E. Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome. PLoS One. 2019 Jan 17;14(1):e0209984. doi: 10.1371/journal.pone.0209984. PMID: 30653533; PMCID: PMC6336311. 5: Hagerman R, Jacquemont S, Berry-Kravis E, Des Portes V, Stanfield A, Koumaras B, Rosenkranz G, Murgia A, Wolf C, Apostol G, von Raison F. Mavoglurant in Fragile X Syndrome: Results of two open-label, extension trials in adults and adolescents. Sci Rep. 2018 Nov 19;8(1):16970. doi: 10.1038/s41598-018-34978-4. PMID: 30451888; PMCID: PMC6242849. 6: Yilmaz Y, Umehara K, Williams G, Faller T, Schiller H, Walles M, Kraehenbuehl S, Camenisch G, Manevski N. Assessment of the pulmonary CYP1A1 metabolism of mavoglurant (AFQ056) in rat. Xenobiotica. 2018 Aug;48(8):793-803. doi: 10.1080/00498254.2017.1373311. Epub 2017 Sep 29. PMID: 28879796. 7: Rouzade-Dominguez ML, Pezous N, David OJ, Tutuian R, Bruley des Varannes S, Tack J, Malfertheiner P, Allescher HD, Ufer M, Rühl A. The selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056) reduces the incidence of reflux episodes in dogs and patients with moderate to severe gastroesophageal reflux disease. Neurogastroenterol Motil. 2017 Aug;29(8). doi: 10.1111/nmo.13058. Epub 2017 Mar 23. PMID: 28337838. 8: Rutrick D, Stein DJ, Subramanian G, Smith B, Fava M, Hasler G, Cha JH, Gasparini F, Donchev T, Ocwieja M, Johns D, Gomez-Mancilla B. Mavoglurant Augmentation in OCD Patients Resistant to Selective Serotonin Reuptake Inhibitors: A Proof-of-Concept, Randomized, Placebo-Controlled, Phase 2 Study. Adv Ther. 2017 Feb;34(2):524-541. doi: 10.1007/s12325-016-0468-5. Epub 2017 Jan 2. PMID: 28044255. 9: Ufer M, Sagkriotis A, Salunke A, Ganesan S, Tisserant A, Dodman A, Voltz E, Woessner R, Jordaan P, Legangneux E. Intravenous Dosing as an Alternate Approach to Safely Achieve Supratherapeutic Exposure for Assessments of Cardiac Repolarization: A Randomized Clinical Trial with Mavoglurant (AFQ056). Clin Ther. 2016 Dec;38(12):2589-2597. doi: 10.1016/j.clinthera.2016.10.007. Epub 2016 Nov 4. PMID: 27823869. 10: Trenkwalder C, Stocchi F, Poewe W, Dronamraju N, Kenney C, Shah A, von Raison F, Graf A. Mavoglurant in Parkinson's patients with l-Dopa-induced dyskinesias: Two randomized phase 2 studies. Mov Disord. 2016 Jul;31(7):1054-8. doi: 10.1002/mds.26585. Epub 2016 May 23. PMID: 27214258. 11: Bailey DB Jr, Berry-Kravis E, Wheeler A, Raspa M, Merrien F, Ricart J, Koumaras B, Rosenkranz G, Tomlinson M, von Raison F, Apostol G. Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression- Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study. J Neurodev Disord. 2016;8:1. doi: 10.1186/s11689-015-9134-5. Epub 2015 Dec 15. PMID: 26855682; PMCID: PMC4743124. 12: Berry-Kravis E, Des Portes V, Hagerman R, Jacquemont S, Charles P, Visootsak J, Brinkman M, Rerat K, Koumaras B, Zhu L, Barth GM, Jaecklin T, Apostol G, von Raison F. Mavoglurant in fragile X syndrome: Results of two randomized, double- blind, placebo-controlled trials. Sci Transl Med. 2016 Jan 13;8(321):321ra5. doi: 10.1126/scitranslmed.aab4109. PMID: 26764156. 13: Wendling T, Dumitras S, Ogungbenro K, Aarons L. Application of a Bayesian approach to physiological modelling of mavoglurant population pharmacokinetics. J Pharmacokinet Pharmacodyn. 2015 Dec;42(6):639-57. doi: 10.1007/s10928-015-9430-4. Epub 2015 Aug 1. PMID: 26231433. 14: Sivasubramanian R, Chakraborty A, Rouzade-Dominguez ML, Neelakantham S, Jakab A, Mensinga T, Legangneux E, Woessner R, Ufer M. Effect of mavoglurant (AFQ056), a selective mGluR5 antagonist, on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and levonorgestrel in healthy women. Int J Clin Pharmacol Ther. 2015 Jul;53(7):550-6. doi: 10.5414/CP202321. PMID: 25943176. 15: Wendling T, Ogungbenro K, Pigeolet E, Dumitras S, Woessner R, Aarons L. Model-based evaluation of the impact of formulation and food intake on the complex oral absorption of mavoglurant in healthy subjects. Pharm Res. 2015 May;32(5):1764-78. doi: 10.1007/s11095-014-1574-1. Epub 2014 Nov 26. PMID: 25425054. 16: Vranesic I, Ofner S, Flor PJ, Bilbe G, Bouhelal R, Enz A, Desrayaud S, McAllister K, Kuhn R, Gasparini F. AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: identification, SAR and pharmacological characterization. Bioorg Med Chem. 2014 Nov 1;22(21):5790-803. doi: 10.1016/j.bmc.2014.09.033. Epub 2014 Sep 20. PMID: 25316499. 17: Petrov D, Pedros I, de Lemos ML, Pallàs M, Canudas AM, Lazarowski A, Beas- Zarate C, Auladell C, Folch J, Camins A. Mavoglurant as a treatment for Parkinson's disease. Expert Opin Investig Drugs. 2014 Aug;23(8):1165-79. doi: 10.1517/13543784.2014.931370. Epub 2014 Jun 24. PMID: 24960254. 18: Gomez-Mancilla B, Berry-Kravis E, Hagerman R, von Raison F, Apostol G, Ufer M, Gasparini F, Jacquemont S. Development of mavoglurant and its potential for the treatment of fragile X syndrome. Expert Opin Investig Drugs. 2014 Jan;23(1):125-34. doi: 10.1517/13543784.2014.857400. Epub 2013 Nov 20. PMID: 24251408. 19: Kumar R, Hauser RA, Mostillo J, Dronamraju N, Graf A, Merschhemke M, Kenney C. Mavoglurant (AFQ056) in combination with increased levodopa dosages in Parkinson's disease patients. Int J Neurosci. 2016;126(1):20-4. doi: 10.3109/00207454.2013.841685. Epub 2015 Aug 18. PMID: 24007304. 20: Walles M, Wolf T, Jin Y, Ritzau M, Leuthold LA, Krauser J, Gschwind HP, Carcache D, Kittelmann M, Ocwieja M, Ufer M, Woessner R, Chakraborty A, Swart P. Metabolism and disposition of the metabotropic glutamate receptor 5 antagonist (mGluR5) mavoglurant (AFQ056) in healthy subjects. Drug Metab Dispos. 2013 Sep;41(9):1626-41. doi: 10.1124/dmd.112.050716. Epub 2013 Jun 17. PMID: 23775850.