Mavoglurant

Mavoglurant, aslo known as AFQ056, is an experimental drug candidate for the treatment of fragile X syndrome. Mavoglurant exerts its effect as an antagonist of the metabotropic glutamate receptor 5 (mGLU5). Novartis discontinued development of mavoglurant for fragile X syndrome in April 2014 following disappointing trial results. Currently Novartis is conducting a clinical trial with this drug on obsessive compulsive disorder.

Product information

CAS Number: 543906-09-8

Molecular Weight: 313.39

Formula: C19H23NO3

Synonym:

AFQ-056

AFQ 056

AFQ056

Mavoglurant

Chemical Name: methyl(3aR,4S,7aR)-4-hydroxy-4-(m-tolylethynyl)octahydro-1H-indole-1-carboxylate

Smiles: CC1C=C(C=CC=1)C#C[C@]1(O)CCC[C@@H]2[C@H]1CCN2C(=O)OC

InChiKey: ZFPZEYHRWGMJCV-ZHALLVOQSA-N

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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Mavoglurant (1 nM-10 μM; 10 min) fully antagonizes hmGluR5-mediated responses with IC50s of 110 and 30 nM in Ca2+- and PI-turnover assays in L(tk-) cells stably expressing mGluR5a. Mavoglurant (0.01 nM-10 μM) displaces the binding of the allosteric binding ligand [3H]-AAE327 in a concentration-dependent manner in rat brain membranes, with an IC50 of 47 nM.

In Vivo:

Mavoglurant (0.1-10 mg/kg; a single p.o.) inhibits the stress-induced hyperthermia (SIH) in a dose-dependent manner in mice. Mavoglurant (9.4 mg/kg; a single p.o.) exhibits moderate oral bioavailability (32%), terminal half-life (2.9 h) and Cmax (plasma; brain) (950 pmol/mL; 3500 pmol/g). Mavoglurant (3.1 mg/kg; a single i.v.) exhibits terminal half-life (0.69 h), Cmax (plasma; brain) (3330 pmol/mL; 8400 pmol/g) and Tmax (≤0.08 h).

References:

1. 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. PubMed PMID: 26764156.
2. 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. PubMed PMID: 26231433.
3. 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. PubMed PMID: 25943176.

Products are for research use only. Not for human use.