Wikipedia

Mavoglurant

Mavoglurant (developmental code name AFQ-056) is an experimental drug candidate for the treatment of fragile X syndrome and other conditions.[1][2] It exerts its effect as an antagonist of the metabotropic glutamate receptor 5 (mGluR5).[3][4][5]

Mavoglurant
Names
Preferred IUPAC name
Methyl (3aR,4S,7aR)-4-hydroxy-4-[(3-methylphenyl)ethynyl]octahydro-1H-indole-1-carboxylate
Other names
AFQ056
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.219.728 Edit this at Wikidata
UNII
  • 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
    Key: ZFPZEYHRWGMJCV-ZHALLVOQSA-N
  • InChI=1/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
    Key: ZFPZEYHRWGMJCV-ZHALLVOQBN
  • O=C(OC)N3[C@@H]2CCC[C@@](O)(C#Cc1cccc(c1)C)[C@@H]2CC3
Properties
C19H23NO3
Molar mass 313.397 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Mavoglurant was under development by Novartis and reached phase II and phase III clinical trials.[2][6] Phase IIb/III dose finding and evaluation trials for fragile X-syndrome were discontinued by the end of 2014.[7] Otherwise, it would have been the first drug to treat the underlying disorder instead of the symptoms of fragile X syndrome.[8] Mavoglurant was also in phase II clinical trials for Levodopa-induced dyskinesia.[9][10] In 2007, Norvartis had conducted a clinical study to assess its ability of reducing cigarette smoking, but no results had been published up till now.[11] Novartis was conducting a clinical trial with this drug on obsessive–compulsive disorder.[12]

Novartis discontinued development of mavoglurant for fragile X syndrome in April 2014 following disappointing trial results.[7] Development was discontinued for other indications by 2017.[1]

Recently, Stalicla, a biotech company applying artificial intelligence to identify subgroups of high-responder patients, acquired worldwide rights from Novartis to progress the drug for substance-use and neurodevelopmental disorders.[13] [14][15]

See also

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References

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  1. ^ a b "Mavoglurant". AdisInsight. Springer Nature Switzerland AG.
  2. ^ a b Cole P (2012). "Mavoglurant". Drugs of the Future. 37 (1): 7–12. doi:10.1358/dof.2012.037.01.1772147. S2CID 258330291.
  3. ^ Levenga J, Hayashi S, de Vrij FM, Koekkoek SK, van der Linde HC, Nieuwenhuizen I, et al. (June 2011). "AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome". Neurobiology of Disease. 42 (3): 311–317. doi:10.1016/j.nbd.2011.01.022. PMID 21316452. S2CID 45389434.
  4. ^ Arsova A, Møller TC, Vedel L, Hansen JL, Foster SR, Gregory KJ, Bräuner-Osborne H (July 2020). "Detailed In Vitro Pharmacological Characterization of Clinically Tested Negative Allosteric Modulators of the Metabotropic Glutamate Receptor 5". Molecular Pharmacology. 98 (1): 49–60. doi:10.1124/mol.119.119032. PMC 7705108. PMID 32358164.
  5. ^ Witkin JM, Pandey KP, Smith JL (September 2022). "Clinical investigations of compounds targeting metabotropic glutamate receptors". Pharmacology, Biochemistry, and Behavior. 219: 173446. doi:10.1016/j.pbb.2022.173446. PMID 35987339. S2CID 251600367.
  6. ^ Jacquemont S, Curie A, des Portes V, Torrioli MG, Berry-Kravis E, Hagerman RJ, et al. (January 2011). "Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056". Science Translational Medicine. 3 (64): 64ra1. doi:10.1126/scitranslmed.3001708. PMID 21209411. S2CID 206677267.
  7. ^ a b "Novartis Discontinues Development of mavoglurant (AFQ056) for Fragile X Syndrome". Fragile X Research. FRAXA Research Foundation. 2014-04-24.
  8. ^ "AFQ056 drug improves symptoms in Fragile X patients: Study". news-medical.net. January 9, 2011.
  9. ^ Kumar R, Hauser RA, Mostillo J, Dronamraju N, Graf A, Merschhemke M, Kenney C (Sep 2013). "Mavoglurant (AFQ056) in combination with increased levodopa dosages in Parkinson's disease patients". The International Journal of Neuroscience. 126 (1): 20–24. doi:10.3109/00207454.2013.841685. PMID 24007304. S2CID 7531940.
  10. ^ "AFQ056 & Parkinson Search". ClincalTrials.gov. U.S. National Library of Medicine.
  11. ^ Clinical trial number NCT00414752 for "Effects of AFQ056 and Nicotine in Reducing Cigarette Smoking" at ClinicalTrials.gov
  12. ^ Clinical trial number NCT01813019 for "Study to Evaluate the Effect of AFQ056 in Obsessive Compulsive Disorder (OCD)" at ClinicalTrials.gov
  13. ^ LaHucik K (2023-01-09). "Novartis offloads neurodevelopmental disorder asset to small Swiss biotech". Endpoints News.
  14. ^ "Stalicla Inks Mavoglurant Deal With Novartis". Inside Precision Medicine; Genetic Engineering & Biotechnology News. Mary Ann Liebert. 2023-01-12.
  15. ^ "STALICLA attracts US partner for Phase 3 development of anti-cocaine drug". Startupticker Foundation. 2023-03-13.
 

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