Target Information
Target General Infomation | |||||
---|---|---|---|---|---|
Target ID |
T99402
|
||||
Former ID |
TTDR00965
|
||||
Target Name |
Metabotropic glutamate receptor 4
|
||||
Gene Name |
GRM4
|
||||
Synonyms |
Group III metabotropic glutamate receptor 4; mGluR4; GRM4
|
||||
Target Type |
Research
|
||||
Disease | Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42] | ||||
Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89] | |||||
Function |
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.
|
||||
BioChemical Class |
GPCR glutamate
|
||||
Target Validation |
T99402
|
||||
UniProt ID | |||||
Sequence |
MPGKRGLGWWWARLPLCLLLSLYGPWMPSSLGKPKGHPHMNSIRIDGDITLGGLFPVHGR
GSEGKPCGELKKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSL TFVQALIEKDGTEVRCGSGGPPIITKPERVVGVIGASGSSVSIMVANILRLFKIPQISYA STAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQ KSREDGGVCIAQSVKIPREPKAGEFDKIIRRLLETSNARAVIIFANEDDIRRVLEAARRA NQTGHFFWMGSDSWGSKIAPVLHLEEVAEGAVTILPKRMSVRGFDRYFSSRTLDNNRRNI WFAEFWEDNFHCKLSRHALKKGSHVKKCTNRERIGQDSAYEQEGKVQFVIDAVYAMGHAL HAMHRDLCPGRVGLCPRMDPVDGTQLLKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQY QLRNDSAEYKVIGSWTDHLHLRIERMHWPGSGQQLPRSICSLPCQPGERKKTVKGMPCCW HCEPCTGYQYQVDRYTCKTCPYDMRPTENRTGCRPIPIIKLEWGSPWAVLPLFLAVVGIA ATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLG LGMSISYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVV DPSHSVVDFQDQRTLDPRFARGVLKCDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPET FNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQTTTLTVSVSLSASVSLGMLYMP KVYIILFHPEQNVPKRKRSLKAVVTAATMSNKFTQKGNFRPNGEAKSELCENLEAPALAT KQTYVTYTNHAI |
||||
Inhibitor | (2S,1'R,2'S)-2-(2'-phosphonocyclopropyl)glycine | Drug Info | [528723] | ||
GLUTAMATE | Drug Info | [528723] | |||
L-1-amino-4-phosphonobutanoic acid | Drug Info | [528723] | |||
Agonist | (S)-3,4-DCPG | Drug Info | [525960] | ||
ACPT-I | Drug Info | [534471] | |||
FP0429 | Drug Info | [528577] | |||
L-AP4 | Drug Info | [525456] | |||
L-CCG-I | Drug Info | [526752] | |||
L-serine-O-phosphate | Drug Info | [533900] | |||
LSP1-2111 | Drug Info | [530212] | |||
LSP4-2022 | Drug Info | [531757] | |||
[3H]AP4 | Drug Info | [525456] | |||
Modulator | ADX-88178 | Drug Info | [543749] | ||
DT-1687 | Drug Info | [543749] | |||
Modulator (allosteric modulator) | compound 1 | Drug Info | [531863] | ||
compound 11 | Drug Info | [531039] | |||
compound 22a | Drug Info | [531523] | |||
compound 7 | Drug Info | [531039] | |||
Lu AF21934 | Drug Info | [531872] | |||
MPEP | Drug Info | [526594] | |||
PHCCC | Drug Info | [526858] | |||
VU0001171 | Drug Info | [529883] | |||
VU0092145 | Drug Info | [529883] | |||
VU0155041 | Drug Info | [529617] | |||
VU0359516 | Drug Info | [530991] | |||
VU0361737 | Drug Info | [530167] | |||
VU0364770 | Drug Info | [531700] | |||
VU0400195 | Drug Info | [531644] | |||
Antagonist | CPPG | Drug Info | [525456] | ||
MAP4 | Drug Info | [525456] | |||
MPPG | Drug Info | [525456] | |||
Pathways | |||||
KEGG Pathway | Neuroactive ligand-receptor interaction | ||||
Glutamatergic synapse | |||||
Taste transduction | |||||
PANTHER Pathway | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | ||||
Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway | |||||
Metabotropic glutamate receptor group III pathway | |||||
Reactome | G alpha (i) signalling events | ||||
Class C/3 (Metabotropic glutamate/pheromone receptors) | |||||
WikiPathways | GPCRs, Class C Metabotropic glutamate, pheromone | ||||
GPCR ligand binding | |||||
GPCR downstream signaling | |||||
References | |||||
Ref 525456 | Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor. J Biol Chem. 1999 Apr 9;274(15):10008-13. | ||||
Ref 525960 | (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. Neuropharmacology. 2001 Mar;40(3):311-8. | ||||
Ref 526594 | Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP. Br J Pharmacol. 2003 Mar;138(6):1026-30. | ||||
Ref 526752 | Agonist analysis of 2-(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells. Br J Pharmacol. 1992 Oct;107(2):539-43. | ||||
Ref 526858 | (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection. Neuropharmacology. 2003 Dec;45(7):895-906. | ||||
Ref 528577 | Amino-pyrrolidine tricarboxylic acids give new insight into group III metabotropic glutamate receptor activation mechanism. Mol Pharmacol. 2007 Mar;71(3):704-12. Epub 2006 Dec 13. | ||||
Ref 528723 | Bioorg Med Chem. 2007 May 1;15(9):3161-70. Epub 2007 Feb 22.Synthesis and preliminary pharmacological evaluation of the four stereoisomers of (2S)-2-(2'-phosphono-3'-phenylcyclopropyl)glycine, the first class of 3'-substituted trans C1'-2'-2-(2'-phosphonocyclopropyl)glycines. | ||||
Ref 529617 | Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4. Mol Pharmacol. 2008 Nov;74(5):1345-58. | ||||
Ref 529883 | Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead. Bioorg Med Chem Lett. 2009 Feb 1;19(3):962-6. | ||||
Ref 530167 | Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs). J Med Chem. 2009 Jul 23;52(14):4115-8. | ||||
Ref 530212 | Electrophysiological and behavioral evidence that modulation of metabotropic glutamate receptor 4 with a new agonist reverses experimental parkinsonism. FASEB J. 2009 Oct;23(10):3619-28. | ||||
Ref 530991 | Re-exploration of the PHCCC Scaffold: Discovery of Improved Positive Allosteric Modulators of mGluR4. ACS Chem Neurosci. 2010 Jun 16;1(6):411-419. | ||||
Ref 531039 | An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction. Bioorg Med Chem Lett. 2010 Aug 15;20(16):4901-5. | ||||
Ref 531523 | Tricyclic thiazolopyrazole derivatives as metabotropic glutamate receptor 4 positive allosteric modulators. J Med Chem. 2011 Jul 28;54(14):5070-81. | ||||
Ref 531644 | 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. J Med Chem. 2011 Nov 10;54(21):7639-47. | ||||
Ref 531700 | 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. J Pharmacol Exp Ther. 2012 Feb;340(2):404-21. | ||||
Ref 531757 | A novel selective metabotropic glutamate receptor 4 agonist reveals new possibilities for developing subtype selective ligands with therapeutic potential. FASEB J. 2012 Apr;26(4):1682-93. | ||||
Ref 531863 | 4-(1-Phenyl-1H-pyrazol-4-yl)quinolines as novel, selective and brain penetrant metabotropic glutamate receptor 4 positive allosteric modulators. Bioorg Med Chem Lett. 2012 May 1;22(9):3235-9. | ||||
Ref 531872 | Synergy between L-DOPA and a novel positive allosteric modulator of metabotropic glutamate receptor 4: implications for Parkinson's disease treatment and dyskinesia. Neuropharmacology. 2013 Mar;66:158-69. | ||||
Ref 533900 | Serine-O-phosphate has affinity for type IV, but not type I, metabotropic glutamate receptor. Neuroreport. 1993 Sep;4(9):1099-101. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.