Metabotropic glutamate receptor 4

Ligands

Orthosteric

• Cinnabarinic acid, a tryptophan metabolite
• LSP1-2111: agonist
• LSP4-2022: agonist
• LSP2-9166: mixed agonist at mGluR4 and mGluR7

Positive allosteric modulators (PAMs)

• ADX88178
• Foliglurax (PXT-002331, DT-1687)
• Tricyclic thiazolopyrazole derivative 22a: EC50 = 9 nM, Emax = 120%
• ML-128: EC50 = 240 nM, Emax = 182%
• Valiglurax (AP-472) (VU0652957)
• VU-0418506
• VU-001171: EC50 = 650 nM, Emax = 141%, 36-fold shift
• VU0155041: subtype-selective PAM, intrinsic allosteric agonist activity, robust in-vivo activity
• VU0364770
• PHCCC: PAM of mGluR4, negative allosteric modulator of mGluR1, direct agonist at mGluR6
• TC-N 22A

References

References

1. (April 1996). "Molecular characterization and localization of human metabotropic glutamate receptor type 4". Brain Research. Molecular Brain Research.
2. (January 1998). "Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells". Brain Research. Molecular Brain Research.
3. "Entrez Gene: GRM4 glutamate receptor, metabotropic 4".
4. (February 2000). "A metabotropic glutamate receptor variant functions as a taste receptor". Nature Neuroscience.
5. (May 2012). "Cinnabarinic acid, an endogenous metabolite of the kynurenine pathway, activates type 4 metabotropic glutamate receptors". Molecular Pharmacology.
6. (December 2010). "Metabotropic glutamate receptor 4 novel agonist LSP1-2111 with anxiolytic, but not antidepressant-like activity, mediated by serotonergic and GABAergic systems". Neuropharmacology.
7. (April 2012). "A novel selective metabotropic glutamate receptor 4 agonist reveals new possibilities for developing subtype selective ligands with therapeutic potential". FASEB Journal.
8. (July 2011). "Tricyclic thiazolopyrazole derivatives as metabotropic glutamate receptor 4 positive allosteric modulators". Journal of Medicinal Chemistry.
9. (2010). "Discovery of a potent, selective and in vivo active mGluR4 positive allosteric modulator". Probe Reports from the NIH Molecular Libraries Program [Internet].
10. (July 2009). "Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs)". Journal of Medicinal Chemistry.
11. (March 2019). "Discovery of VU2957 (Valiglurax): An mGlu₄ Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease". ACS Medicinal Chemistry Letters.
12. (September 2016). "Development and Antiparkinsonian Activity of VU0418506, a Selective Positive Allosteric Modulator of Metabotropic Glutamate Receptor 4 Homomers without Activity at mGlu2/4 Heteromers". ACS Chemical Neuroscience.
13. (September 2016). "Discovery, Synthesis, and Preclinical Characterization of N-(3-Chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506), a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu4)". ACS Chemical Neuroscience.
14. (February 2009). "Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead". Bioorganic & Medicinal Chemistry Letters.
15. (November 2008). "Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4". Molecular Pharmacology.
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17. (July 2008). "The mGlu(4) receptor allosteric modulator N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide acts as a direct agonist at mGlu(6) receptors". European Journal of Pharmacology.