Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0IFKL)

• DTT Name: Metabotropic glutamate receptor 8 (mGluR8)
• Synonyms: MGluR8a; MGLUR8; Glutamate receptor mGLU8; GRM8
• Gene Name: GRM8
• DTT Type: Literature-reported target; [1]
• BioChemical Class: GPCR glutamate
• UniProt ID: GRM8_HUMAN
• TTD ID: T77548
• Sequence:
  MVCEGKRSASCPCFFLLTAKFYWILTMMQRTHSQEYAHSIRVDGDIILGGLFPVHAKGER
  GVPCGELKKEKGIHRLEAMLYAIDQINKDPDLLSNITLGVRILDTCSRDTYALEQSLTFV
  QALIEKDASDVKCANGDPPIFTKPDKISGVIGAAASSVSIMVANILRLFKIPQISYASTA
  PELSDNTRYDFFSRVVPPDSYQAQAMVDIVTALGWNYVSTLASEGNYGESGVEAFTQISR
  EIGGVCIAQSQKIPREPRPGEFEKIIKRLLETPNARAVIMFANEDDIRRILEAAKKLNQS
  GHFLWIGSDSWGSKIAPVYQQEEIAEGAVTILPKRASIDGFDRYFRSRTLANNRRNVWFA
  EFWEENFGCKLGSHGKRNSHIKKCTGLERIARDSSYEQEGKVQFVIDAVYSMAYALHNMH
  KDLCPGYIGLCPRMSTIDGKELLGYIRAVNFNGSAGTPVTFNENGDAPGRYDIFQYQITN
  KSTEYKVIGHWTNQLHLKVEDMQWAHREHTHPASVCSLPCKPGERKKTVKGVPCCWHCER
  CEGYNYQVDELSCELCPLDQRPNMNRTGCQLIPIIKLEWHSPWAVVPVFVAILGIIATTF
  VIVTFVRYNDTPIVRASGRELSYVLLTGIFLCYSITFLMIAAPDTIICSFRRVFLGLGMC
  FSYAALLTKTNRIHRIFEQGKKSVTAPKFISPASQLVITFSLISVQLLGVFVWFVVDPPH
  IIIDYGEQRTLDPEKARGVLKCDISDLSLICSLGYSILLMVTCTVYAIKTRGVPETFNEA
  KPIGFTMYTTCIIWLAFIPIFFGTAQSAEKMYIQTTTLTVSMSLSASVSLGMLYMPKVYI
  IIFHPEQNVQKRKRSFKAVVTAATMQSKLIQKGNDRPNGEVKSELCESLETNTSSTKTTY
  ISYSNHSI
• Function: Receptor for glutamate. The activity of this receptor is mediated by a g-protein that inhibits adenylate cyclase activity.
• 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

15 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]
(R,S)-4-phosphonophenylglycine	DM7COSH	Discovery agent	N.A.	Investigative	[2]
(S)-3,4-DCPG	DMG5BUA	Discovery agent	N.A.	Investigative	[3]
2-Amino-4-phosphono-butyric acid	DMOIZY1	Discovery agent	N.A.	Investigative	[4]
ACPT-I	DM264XN	Discovery agent	N.A.	Investigative	[5]
alpha-methylserine-O-phosphate	DMCIH1X	Discovery agent	N.A.	Investigative	[6]
AZ12216052	DM1IN35	Discovery agent	N.A.	Investigative	[7]
CPPG	DMVHX5T	Discovery agent	N.A.	Investigative	[8]
D-AP4	DM2WS8B	Discovery agent	N.A.	Investigative	[1]
L-AP4	DMPJFGI	Discovery agent	N.A.	Investigative	[9], [10]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[9]
L-serine-O-phosphate	DMTJ1NH	Discovery agent	N.A.	Investigative	[9]
MAP4	DMUCE93	Discovery agent	N.A.	Investigative	[8]
MPPG	DMJHQ9T	Discovery agent	N.A.	Investigative	[1]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[11]

References

• [1] Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells. Brain Res Mol Brain Res. 1998 Jan;53(1-2):88-97.
• [2] Anticonvulsant activity of a metabotropic glutamate receptor 8 preferential agonist, (R,S)-4-phosphonophenylglycine. Eur J Pharmacol. 1999 Oct 21;383(1):23-7.
• [3] (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.
• [4] (2S,1'S,2'R,3'R)-2(2'-Carboxy-3'-hydroxymethylcyclopropyl)glycine-[3H], a potent and selective radioligand for labeling group 2 and 3 metabotropic ... Bioorg Med Chem Lett. 2005 Jan 17;15(2):349-51.
• [5] Pharmacological characterization of the rat metabotropic glutamate receptor type 8a revealed strong similarities and slight differences with the type 4a receptor. Eur J Pharmacol. 2000 Apr 7;394(1):17-26.
• [6] The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr Drug Targets CNS Neurol Disord. 2002 Jun;1(3):297-317.
• [7] Acute pharmacological modulation of mGluR8 reduces measures of anxiety. Behav Brain Res. 2010 Oct 15;212(2):168-73.
• [8] Constraints on proper folding of the amino terminal domains of group III metabotropic glutamate receptors. Brain Res Mol Brain Res. 2000 Mar 10;76(1):180-90.
• [9] Cloning and functional expression of alternative spliced variants of the human metabotropic glutamate receptor 8. Brain Res Mol Brain Res. 1999 Apr 20;67(2):201-10.
• [10] Synthesis and preliminary pharmacological evaluation of the four stereoisomers of (2S)-2-(2'-phosphono-3'-phenylcyclopropyl)glycine, the first clas... Bioorg Med Chem. 2007 May 1;15(9):3161-70.
• [11] Excitatory amino acid receptor ligands: resolution, absolute stereochemistry, and enantiopharmacology of 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)... J Med Chem. 1998 Mar 12;41(6):930-9.