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
CAS Number	543906-09-8 Y
3D model (JSmol)	Interactive image
ChemSpider	8102466
ECHA InfoCard	100.219.728
IUPHAR/BPS	7586
PubChem CID	9926832
UNII	GT0I9SV4F6
CompTox Dashboard (EPA)	DTXSID30202777
InChI 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
SMILES O=C(OC)N3[C@@H]2CCC[C@@](O)(C#Cc1cccc(c1)C)[C@@H]2CC3
Properties
Chemical formula	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). Infobox references

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

• Basimglurant

References

1. "Mavoglurant". AdisInsight. Springer Nature Switzerland AG.
2. 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. "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.