Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWRP2F)

• DTT Name: Metabotropic glutamate receptor 6 (mGluR6)
• Synonyms: MGLUR6; GPRC1F
• Gene Name: GRM6
• DTT Type: Literature-reported target; [1]
• BioChemical Class: GPCR glutamate
• UniProt ID: GRM6_HUMAN
• TTD ID: T55956
• Sequence:
  MARPRRAREPLLVALLPLAWLAQAGLARAAGSVRLAGGLTLGGLFPVHARGAAGRACGQL
  KKEQGVHRLEAMLYALDRVNADPELLPGVRLGARLLDTCSRDTYALEQALSFVQALIRGR
  GDGDEVGVRCPGGVPPLRPAPPERVVAVVGASASSVSIMVANVLRLFAIPQISYASTAPE
  LSDSTRYDFFSRVVPPDSYQAQAMVDIVRALGWNYVSTLASEGNYGESGVEAFVQISREA
  GGVCIAQSIKIPREPKPGEFSKVIRRLMETPNARGIIIFANEDDIRRVLEAARQANLTGH
  FLWVGSDSWGAKTSPILSLEDVAVGAITILPKRASIDGFDQYFMTRSLENNRRNIWFAEF
  WEENFNCKLTSSGTQSDDSTRKCTGEERIGRDSTYEQEGKVQFVIDAVYAIAHALHSMHQ
  ALCPGHTGLCPAMEPTDGRMLLQYIRAVRFNGSAGTPVMFNENGDAPGRYDIFQYQATNG
  SASSGGYQAVGQWAETLRLDVEALQWSGDPHEVPSSLCSLPCGPGERKKMVKGVPCCWHC
  EACDGYRFQVDEFTCEACPGDMRPTPNHTGCRPTPVVRLSWSSPWAAPPLLLAVLGIVAT
  TTVVATFVRYNNTPIVRASGRELSYVLLTGIFLIYAITFLMVAEPGAAVCAARRLFLGLG
  TTLSYSALLTKTNRIYRIFEQGKRSVTPPPFISPTSQLVITFSLTSLQVVGMIAWLGARP
  PHSVIDYEEQRTVDPEQARGVLKCDMSDLSLIGCLGYSLLLMVTCTVYAIKARGVPETFN
  EAKPIGFTMYTTCIIWLAFVPIFFGTAQSAEKIYIQTTTLTVSLSLSASVSLGMLYVPKT
  YVILFHPEQNVQKRKRSLKATSTVAAPPKGEDAEAHK
• 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, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity (By similarity). Signaling stimulates TRPM1 channel activity and Ca(2+) uptake. Required for normal vision.
• KEGG Pathway:
  Phospholipase D signaling pathway (hsa04072)
  Neuroactive ligand-receptor interaction (hsa04080)
  Glutamatergic synapse (hsa04724)
• Reactome Pathway:
  Class C/3 (Metabotropic glutamate/pheromone receptors) (R-HSA-420499)
  G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DTT

16 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[1]
(S)-3,4-DCPG	DMG5BUA	Discovery agent	N.A.	Investigative	[2]
1-benzyl-APDC	DMJHXMY	Discovery agent	N.A.	Investigative	[1]
ACPT-I	DM264XN	Discovery agent	N.A.	Investigative	[1]
alpha-methylserine-O-phosphate	DMCIH1X	Discovery agent	N.A.	Investigative	[3]
homo-AMPA	DMH96AI	Discovery agent	N.A.	Investigative	[4]
L-AP4	DMPJFGI	Discovery agent	N.A.	Investigative	[5]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[6]
L-serine-O-phosphate	DMTJ1NH	Discovery agent	N.A.	Investigative	[5]
LSP1-2111	DM74J10	Discovery agent	N.A.	Investigative	[7]
LSP4-2022	DMBWHGP	Discovery agent	N.A.	Investigative	[8]
MAP4	DMUCE93	Discovery agent	N.A.	Investigative	[3]
MPPG	DMJHQ9T	Discovery agent	N.A.	Investigative	[1]
PHCCC	DMNJY79	Discovery agent	N.A.	Investigative	[9]
THPG	DMD1G6R	Discovery agent	N.A.	Investigative	[10]
[3H]LY341495	DMGX0Y8	Discovery agent	N.A.	Investigative	[11]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 294).
• [2] (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.
• [3] The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr Drug Targets CNS Neurol Disord. 2002 Jun;1(3):297-317.
• [4] A new highly selective metabotropic excitatory amino acid agonist: 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid. J Med Chem. 1996 Aug 2;39(16):3188-94.
• [5] Cloning, distribution and functional expression of the human mGlu6 metabotropic glutamate receptor. Neuropharmacology. 1997 Feb;36(2):145-52.
• [6] Comparative effect of L-CCG-I, DCG-IV and gamma-carboxy-L-glutamate on all cloned metabotropic glutamate receptor subtypes. Neuropharmacology. 1998 Aug;37(8):1043-51.
• [7] 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.
• [8] 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.
• [9] The mGlu(4) receptor allosteric modulator N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide acts as a direct agonist at mGlu(6) receptors. Eur J Pharmacol. 2008 Jul 28;589(1-3):49-52.
• [10] Two phenylglycine derivatives antagonize responses to L-AP4 in ON bipolar cells of the amphibian retina. Neuropharmacology. 1997 Jan;36(1):13-20.
• [11] Binding of [3H](2S,1'S,2'S)-2-(9-xanthylmethyl)-2-(2'-carboxycyclopropyl) glycine ([3H]LY341495) to cell membranes expressing recombinant human group III metabotropic glutamate receptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2000 Dec;362(6):546-54.