Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMGX0Y8)

• Drug Name: [3H]LY341495 Drug Info
• Synonyms: GTVQXKHWYDSDNM-JRHNIRLTSA-N; AC1O44IH; CTK8F0257; AN-16504; (1S,2S)-2-[(2S)-2-amino-3-(2,6-dioxo-3H-purin-9-yl)-1-hydroxy-1-oxopropan-2-yl]cyclopropane-1-carboxylic acid; (1S,2S)-2-[(1S)-1-amino-1-carboxy-2-(2,6-dioxo-3H-purin-9-yl)ethyl]cyclopropanecarboxylic; [3H]alpha-9'-xantheylmethyl-2-(carboxycyclopropyl)glycine; LY341495

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1] , [2]

• Cross-matching ID:
  PubChem CID: 9819927
  ChEBI ID: CHEBI:93224
  CAS Number: CAS 201943-63-7
  TTD Drug ID: DMGX0Y8

Molecule-Related Drug Atlas

Drug(s) Targeting Metabotropic glutamate receptor 3 (mGluR3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY404039	DMWZIRJ	Schizophrenia	6A20	Phase 3	[7]
RO-4995819	DMNTC7O	Major depressive disorder	6A70.3	Phase 2	[8]
Oleoyl-estrone	DM0RA8F	Alzheimer disease	8A20	Phase 2	[9]
MP-101	DMYCITZ	Alzheimer disease	8A20	Phase 2	[10]
BCI-838	DMRXDN3	Major depressive disorder	6A70.3	Phase 1	[11]
Pomaglumetad	DMTOLI5	Schizophrenia	6A20	Phase 1	[12]
BCI-632	DMZYCWT	Alzheimer disease	8A20	Phase 1	[13]
PMID25435285-Compound-16	DMKFX2G	N. A.	N. A.	Patented	[14]
PMID25435285-Compound-15	DMHBWNS	N. A.	N. A.	Patented	[14]
PMID25435285-Compound-20	DMG9FYH	N. A.	N. A.	Patented	[14]

Drug(s) Targeting Metabotropic glutamate receptor 6 (mGluR6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-serine-O-phosphate	DMTJ1NH	Discovery agent	N.A.	Investigative	[15]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[16]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[17]
MAP4	DMUCE93	Discovery agent	N.A.	Investigative	[18]
MPPG	DMJHQ9T	Discovery agent	N.A.	Investigative	[17]
alpha-methylserine-O-phosphate	DMCIH1X	Discovery agent	N.A.	Investigative	[18]
L-AP4	DMPJFGI	Discovery agent	N.A.	Investigative	[15]
PHCCC	DMNJY79	Discovery agent	N.A.	Investigative	[19]
LSP4-2022	DMBWHGP	Discovery agent	N.A.	Investigative	[20]
(S)-3,4-DCPG	DMG5BUA	Discovery agent	N.A.	Investigative	[21]

Drug(s) Targeting Metabotropic glutamate receptor 7 (mGluR7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-serine-O-phosphate	DMTJ1NH	Discovery agent	N.A.	Investigative	[6]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[22]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[6]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[6]
(+)-MCPG	DMG5QJB	Discovery agent	N.A.	Investigative	[6]
MAP4	DMUCE93	Discovery agent	N.A.	Investigative	[6]
MPPG	DMJHQ9T	Discovery agent	N.A.	Investigative	[6]
alpha-methylserine-O-phosphate	DMCIH1X	Discovery agent	N.A.	Investigative	[6]
L-AP4	DMPJFGI	Discovery agent	N.A.	Investigative	[6]
LSP4-2022	DMBWHGP	Discovery agent	N.A.	Investigative	[20]

Drug(s) Targeting Metabotropic glutamate receptor 2 (mGluR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RO-4995819	DMNTC7O	Major depressive disorder	6A70.3	Phase 2	[8]
Oleoyl-estrone	DM0RA8F	Alzheimer disease	8A20	Phase 2	[9]
MP-101	DMYCITZ	Alzheimer disease	8A20	Phase 2	[10]
BCI-838	DMRXDN3	Major depressive disorder	6A70.3	Phase 1	[11]
Pomaglumetad	DMTOLI5	Schizophrenia	6A20	Phase 1	[12]
BCI-632	DMZYCWT	Alzheimer disease	8A20	Phase 1	[13]
LY-2979165	DM16IX2	Bipolar disorder	6A60	Phase 1	[23]
JNJ-42491293	DMOL9JR	Psychiatric disorder	6E8Z	Phase 1	[24]
ADX71149	DMBUOX4	Epilepsy	8A60-8A68	Phase 1	[25]
PMID25435285-Compound-16	DMKFX2G	N. A.	N. A.	Patented	[14]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Metabotropic glutamate receptor 2 (mGluR2)	TTXJ47W	GRM2_HUMAN	Antagonist	[3] , [4]
Metabotropic glutamate receptor 3 (mGluR3)	TT8A9EF	GRM3_HUMAN	Agonist	[5]
Metabotropic glutamate receptor 6 (mGluR6)	TTWRP2F	GRM6_HUMAN	Antagonist	[6]
Metabotropic glutamate receptor 7 (mGluR7)	TT0I76D	GRM7_HUMAN	Antagonist	[6]

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. (Ligand id: 1399).
• [2] 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. (Ligand id: 1378).
• [3] [3H]-LY341495 as a novel antagonist radioligand for group II metabotropic glutamate (mGlu) receptors: characterization of binding to membranes of mGlu receptor subtype expressing cells. Neuropharmacology. 1999 Oct;38(10):1519-29.
• [4] Group II metabotropic glutamate receptors within the amygdala regulate fear as assessed with potentiated startle in rats. Behav Neurosci. 2002 Dec;116(6):1075-83.
• [5] Characterization of [(3)H]-LY354740 binding to rat mGlu2 and mGlu3 receptors expressed in CHO cells using semliki forest virus vectors. Neuropharmacology. 2000 Jul 24;39(10):1700-6.
• [6] 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.
• [7] Positive allosteric modulators of the metabotropic glutamate receptor 2 for the treatment of schizophrenia. Expert Opin Ther Pat. 2009 Sep;19(9):1259-75.
• [8] Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat. 2013; 9: 1101-1112.
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] ClinicalTrials.gov (NCT03044249) A Study of MP-101 in Dementia-Related Psychosis and/or Agitation and Aggression. U.S. National Institutes of Health.
• [11] Metabotropic glutamate receptor subtype 2 (GRM2; MGLUR2); GRM3 (MGLUR3). SciBX 3(13); doi:10.1038/scibx.2010.413. April 1 2010
• [12] LY-2140023, a prodrug of the group II metabotropic glutamate receptor agonist LY-404039 for the potential treatment of schizophrenia. Curr Opin Investig Drugs. 2010 Jul;11(7):833-45.
• [13] Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists. J Med Chem. 2004 Aug 26;47(18):4570-87.
• [14] Novel metabotropic glutamate receptor 2/3 antagonists and their therapeutic applications: a patent review (2005 - present).Expert Opin Ther Pat. 2015 Jan;25(1):69-90.
• [15] Cloning, distribution and functional expression of the human mGlu6 metabotropic glutamate receptor. Neuropharmacology. 1997 Feb;36(2):145-52.
• [16] 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.
• [17] 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).
• [18] The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr Drug Targets CNS Neurol Disord. 2002 Jun;1(3):297-317.
• [19] 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.
• [20] 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.
• [21] (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.
• [22] 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.
• [23] Annual Reports in Medicinal Chemistry. Volume 47, 2012, Page(78).
• [24] Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders. Nat Rev Drug Discov. 2014 Sep;13(9):692-708.
• [25] MGlu2 receptor-mediated modulation of conditioned avoidance behavior in rats. European journal of pharmacology. 01/2014; 727(1).