Target family: Metabotropic glutamate receptors (type: gpcr)
Target: mGlu<sub>4</sub> receptor

Ligand: ACPT-I (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 5.1 pEC50
Reference (Journal): Synthesis and pharmacological characterization of aminocyclopentanetricarboxylic acids: new tools to discriminate between metabotropic glutamate receptor subtypes.
Published in: J Med Chem

Ligand: ADX88178 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 8.04 pEC50
Reference (Journal): A potent and selective metabotropic glutamate receptor 4 positive allosteric modulator improves movement in rodent models of Parkinson's disease.
Published in: J Pharmacol Exp Ther

Ligand: ADX88178 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 8.5 pEC50
Reference (Journal): A potent and selective metabotropic glutamate receptor 4 positive allosteric modulator improves movement in rodent models of Parkinson's disease.
Published in: J Pharmacol Exp Ther

Ligand: ADX88178 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 7.4 pKi
Reference (Journal): A potent and selective metabotropic glutamate receptor 4 positive allosteric modulator improves movement in rodent models of Parkinson's disease.
Published in: J Pharmacol Exp Ther

Ligand: compound 11 [PMID: 20638279] (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6 pEC50
Reference (Journal): An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction.
Published in: Bioorg Med Chem Lett

Ligand: compound 1 [PMID: 22465637] (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6.7 pEC50
Reference (Journal): 4-(1-Phenyl-1H-pyrazol-4-yl)quinolines as novel, selective and brain penetrant metabotropic glutamate receptor 4 positive allosteric modulators.
Published in: Bioorg Med Chem Lett

Ligand: compound 22a [PMID: 21688779] (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 8.1 pEC50
Reference (Journal): Tricyclic thiazolopyrazole derivatives as metabotropic glutamate receptor 4 positive allosteric modulators.
Published in: J Med Chem

Ligand: compound 7 [PMID: 20638279] (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6 pEC50
Reference (Journal): An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction.
Published in: Bioorg Med Chem Lett

Ligand: CPPG (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 4.6 pKi
Reference (Journal): Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor.
Published in: J Biol Chem

Ligand: foliglurax (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity: 7.119999885559082 pEC50
Reference (Patent): Brain-penetrant chromone oxime derivative for the therapy of levodopa-induced dyskinesia

Ligand: FP0429 (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pEC50
Reference (Journal): Amino-pyrrolidine tricarboxylic acids give new insight into group III metabotropic glutamate receptor activation mechanism.
Published in: Mol Pharmacol

Ligand: (R,S)-4-PPG (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 5.3 pEC50
Reference (Journal): (+)-4-phosphonophenylglycine (PPG) a new group III selective metabotropic glutamate receptor agonist.
Published in: Bioorg Med Chem Lett

Ligand: (R,S)-4-PPG (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 5.3 pEC50
Reference (Journal): (R,S)-4-phosphonophenylglycine, a potent and selective group III metabotropic glutamate receptor agonist is anticonvulsive and neuroprotective<i>in vivo</i>.
Published in: J Pharmacol Exp Ther

Ligand: (S)-3,4-DCPG (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 5.1 pEC50
Reference (Journal): (S)-3,4-DCPG, a potent and selective mGlu8a receptor agonist, activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord.
Published in: Neuropharmacology

Ligand: L-AP4 (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4.
Published in: J Neurosci

Ligand: L-AP4 (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): Cloning and characterization of a metabotropic glutamate receptor, mGluR4b.
Published in: Neuropharmacology

Ligand: L-AP4 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Median affinity: 6.5 pEC50
Reference (Journal): Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells.
Published in: Brain Res Mol Brain Res

Ligand: L-AP4 (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): [3H]-L-2-amino-4-phosphonobutyrate labels a metabotropic glutamate receptor, mGluR4a.
Published in: Br J Pharmacol

Ligand: L-AP4 (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor.
Published in: J Biol Chem

Ligand: L-CCG-I (Synthetic organic)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): Agonist analysis of 2-(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells.
Published in: Br J Pharmacol

Ligand: L-glutamic acid (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Cloning and characterization of a metabotropic glutamate receptor, mGluR4b.
Published in: Neuropharmacology

Ligand: L-glutamic acid (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor.
Published in: J Biol Chem

Ligand: L-glutamic acid (Metabolite)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): New perspectives for the development of selective metabotropic glutamate receptor ligands.
Published in: Eur J Pharmacol

Ligand: L-glutamic acid (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): (S)-homo-AMPA, a specific agonist at the mGlu6 subtype of metabotropic glutamic acid receptors.
Published in: J Med Chem

Ligand: L-glutamic acid (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKi
Reference (Journal): L-2-amino-4-phosphonobutyrate (L-AP4) is an agonist at the type IV metabotropic glutamate receptor which is negatively coupled to adenylate cyclase.
Published in: Eur J Pharmacol

Ligand: L-serine-O-phosphate (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4.
Published in: J Neurosci

Ligand: L-serine-O-phosphate (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): [3H]-L-2-amino-4-phosphonobutyrate labels a metabotropic glutamate receptor, mGluR4a.
Published in: Br J Pharmacol

Ligand: L-serine-O-phosphate (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor.
Published in: J Biol Chem

Ligand: L-serine-O-phosphate (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): Cloning and characterization of a metabotropic glutamate receptor, mGluR4b.
Published in: Neuropharmacology

Ligand: L-serine-O-phosphate (Metabolite)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): Serine-O-phosphate has affinity for type IV, but not type I, metabotropic glutamate receptor.
Published in: Neuroreport

Ligand: L-serine-O-phosphate (Metabolite)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Primary target: no
Median affinity: 5.900000095367432 pEC50
Reference (Journal): Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells.
Published in: Brain Res Mol Brain Res

Ligand: LSP1-2111 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Median affinity: 5.66 pEC50
Reference (Journal): Electrophysiological and behavioral evidence that modulation of metabotropic glutamate receptor 4 with a new agonist reverses experimental parkinsonism.
Published in: FASEB J

Ligand: LSP4-2022 (Synthetic organic)
Interaction type: Agonist
Action: Agonist
Ligand approved: no
Median affinity: 6.96 pEC50
Reference (Journal): A novel selective metabotropic glutamate receptor 4 agonist reveals new possibilities for developing subtype selective ligands with therapeutic potential.
Published in: FASEB J

Ligand: Lu AF21934 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6.3 pEC50
Reference (Journal): Synergy between L-DOPA and a novel positive allosteric modulator of metabotropic glutamate receptor 4: implications for Parkinson's disease treatment and dyskinesia.
Published in: Neuropharmacology

Ligand: LY341495 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 4.7 pIC50
Reference (Journal): Pharmacological analysis of 4-carboxyphenylglycine derivatives: comparison of effects on mGluR1 alpha and mGluR5a subtypes.
Published in: Neuropharmacology

Ligand: MAP4 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 4.6 pKi
Reference (Journal): Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor.
Published in: J Biol Chem

Ligand: MPEP (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP.
Published in: Br J Pharmacol

Ligand: MPPG (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 4.2 pKi
Reference (Journal): Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor.
Published in: J Biol Chem

Ligand: PHCCC (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity: 4.5 pEC50
Reference (Journal): (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection.
Published in: Neuropharmacology

Ligand: SIB-1893 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity:  pEC50
Reference (Journal): Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP.
Published in: Br J Pharmacol

Ligand: VU0001171 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6.2 pEC50
Reference (Journal): Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead.
Published in: Bioorg Med Chem Lett

Ligand: VU0080241 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 5.3 pEC50
Reference (Journal): Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4): Part I. Discovery of pyrazolo[3,4-d]pyrimidines as novel mGluR4 positive allosteric modulators.
Published in: Bioorg Med Chem Lett

Ligand: VU0092145 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity:  pEC50
Reference (Journal): Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead.
Published in: Bioorg Med Chem Lett

Ligand: VU0155041 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: no
Median affinity: 6.099999904632568 pEC50
Reference (Journal): Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4.
Published in: Mol Pharmacol

Ligand: VU0359516 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6.4 pEC50
Reference (Journal): Re-exploration of the PHCCC Scaffold: Discovery of Improved Positive Allosteric Modulators of mGluR4.
Published in: ACS Chem Neurosci

Ligand: VU0361737 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6.6 pEC50
Reference (Journal): Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs).
Published in: J Med Chem

Ligand: VU0364770 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6.5 pEC50
Reference (Journal): The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease.
Published in: J Pharmacol Exp Ther

Ligand: VU0364770 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6 pEC50
Reference (Journal): The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease.
Published in: J Pharmacol Exp Ther

Ligand: VU0400195 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6.5 pEC50
Reference (Journal): Discovery, synthesis, and structure-activity relationship development of a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): characterization of a novel positive allosteric modulator of the metabotropic glutamate receptor 4 (mGlu(4)) with oral efficacy in an antiparkinsonian animal model.
Published in: J Med Chem

Ligand: VU0400195 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Median affinity: 6.4 pEC50
Reference (Journal): Discovery, synthesis, and structure-activity relationship development of a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): characterization of a novel positive allosteric modulator of the metabotropic glutamate receptor 4 (mGlu(4)) with oral efficacy in an antiparkinsonian animal model.
Published in: J Med Chem

Ligand: VU2957 (Synthetic organic)
Interaction type: Allosteric modulator
Action: Positive
Ligand approved: no
Primary target: yes
Median affinity: 7.190000057220459 pEC50
Reference (Journal): Discovery of VU2957 (Valiglurax): An mGlu<sub>4</sub> Positive Allosteric Modulator Evaluated as a Preclinical Candidate for the Treatment of Parkinson's Disease.
Published in: ACS Med Chem Lett