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

General Information of DTT (ID: TTXJ47W)

• DTT Name: Metabotropic glutamate receptor 2 (mGluR2) DTT Info
• Gene Name: GRM2

Molecule-Related Drug & Molecule List

10 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JNJ-64281802	DMNMSVX	Dengue	1D20-1D2Z	Phase 2	[1]
MP-101	DMYCITZ	Alzheimer disease	8A20	Phase 2	[2]
Oleoyl-estrone	DM0RA8F	Alzheimer disease	8A20	Phase 2	[3]
RO-4995819	DMNTC7O	Major depressive disorder	6A70.3	Phase 2	[4]
ADX71149	DMBUOX4	Epilepsy	8A60-8A68	Phase 1	[5]
BCI-632	DMZYCWT	Alzheimer disease	8A20	Phase 1	[6]
BCI-838	DMRXDN3	Major depressive disorder	6A70.3	Phase 1	[7]
JNJ-42491293	DMOL9JR	Psychiatric disorder	6E8Z	Phase 1	[8]
LY-2979165	DM16IX2	Bipolar disorder	6A60	Phase 1	[9]
Pomaglumetad	DMTOLI5	Schizophrenia	6A20	Phase 1	[10]

49 Patented Agent(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethinyl-pyrazole derivative 1	DMLOBAQ	N. A.	N. A.	Patented	[11]
Ethinyl-pyrazole derivative 2	DMA3PE7	N. A.	N. A.	Patented	[11]
Ethinyl-pyrazole derivative 3	DM87DOX	N. A.	N. A.	Patented	[11]
Heteroaryl-pyrazole derivative 1	DM9LQCH	N. A.	N. A.	Patented	[11]
Heteroaryl-pyrazole derivative 2	DMIG0TQ	N. A.	N. A.	Patented	[11]
Heteroaryl-pyrazole derivative 3	DMO45G3	N. A.	N. A.	Patented	[11]
N-substituted pyrazole derivative 1	DMHTVGM	N. A.	N. A.	Patented	[11]
N-substituted pyrazole derivative 2	DMQWODI	N. A.	N. A.	Patented	[11]
N-substituted pyrazole derivative 3	DM5TIFH	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-10	DM12QO7	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-15	DMHBWNS	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-16	DMKFX2G	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-20	DMG9FYH	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-22	DM27U1F	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-25	DMIVJMO	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-26	DMTJHAK	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-37	DMTYHCU	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-38	DMSIKM2	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-39	DMG2ES1	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-40	DMW2C19	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-41	DMJ5LGA	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-42	DMTN79G	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-43	DMEGJ73	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-44	DM4K3AU	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-45	DM74WSJ	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-46	DMC6HPV	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-47	DM92F1C	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-49	DM7G51M	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-50	DML48NA	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-51	DM2VZG6	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-52	DMXD8L1	N. A.	N. A.	Patented	[11]
PMID25435285-Compound-53	DMSRYIP	N. A.	N. A.	Patented	[11]
Pyrazole derivative 76	DM6Y27J	N. A.	N. A.	Patented	[11]
Pyrazole derivative 77	DM5E1ZJ	N. A.	N. A.	Patented	[11]
Pyrazole derivative 78	DMMCHOW	N. A.	N. A.	Patented	[11]
Pyrazole derivative 79	DM9JHYL	N. A.	N. A.	Patented	[11]
Quinoline derivative 3	DMDV6EY	N. A.	N. A.	Patented	[11]
Quinoline derivative 4	DMPB4L6	N. A.	N. A.	Patented	[11]
Quinoline derivative 5	DMS1TOX	N. A.	N. A.	Patented	[11]
Quinoline derivative 6	DMVBPGI	N. A.	N. A.	Patented	[11]
Quinoline derivative 7	DM56I8H	N. A.	N. A.	Patented	[11]
Quinoline derivative 8	DMLIW1X	N. A.	N. A.	Patented	[11]
Quinoline derivative 9	DMIC86N	N. A.	N. A.	Patented	[11]
Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 1	DM3W5SM	N. A.	N. A.	Patented	[11]
Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 2	DMB1T6S	N. A.	N. A.	Patented	[11]
Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 3	DM71LVY	N. A.	N. A.	Patented	[11]
Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 4	DMLMXT6	N. A.	N. A.	Patented	[11]
Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 5	DM7C0R8	N. A.	N. A.	Patented	[11]
Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 6	DMCE3J0	N. A.	N. A.	Patented	[11]

6 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY-544344	DMSC4K1	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[12]
LY-2300559	DMTS1X5	Migraine	8A80	Discontinued in Phase 2	[13]
LY354740	DM08BIZ	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 2	[14]
R-1578	DMAPRGQ	Mood disorder	6A60-6E23	Discontinued in Phase 2	[15]
RG1578	DM3TU7D	Major depressive disorder	6A70.3	Discontinued in Phase 2	[16]
TS-032	DMOHEYU	Schizophrenia	6A20	Discontinued in Phase 1	[17]

37 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+)-MCPG	DMG5QJB	Discovery agent	N.A.	Investigative	[18]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[19]
(2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate	DMYW40T	Discovery agent	N.A.	Investigative	[20]
(S)-4C3HPG	DMQK4I2	Discovery agent	N.A.	Investigative	[18]
3-MPPTS	DMCDLG4	Discovery agent	N.A.	Investigative	[21]
4-APPES	DM1UXHE	Discovery agent	N.A.	Investigative	[21]
4-MPPTS	DM4E6HW	Discovery agent	N.A.	Investigative	[22]
alpha-methylserine-O-phosphate	DMCIH1X	Discovery agent	N.A.	Investigative	[18]
biphenylindanone A	DM2MYKC	Discovery agent	N.A.	Investigative	[23]
CBiPES	DMALVY7	Discovery agent	N.A.	Investigative	[21]
cyPPTS	DME9LPO	Discovery agent	N.A.	Investigative	[21]
DCG IV	DM9HG1Y	Discovery agent	N.A.	Investigative	[24]
DT-2228	DMCKQF7	Major depressive disorder	6A70.3	Investigative	[25]
eGlu	DMKW0Q3	Discovery agent	N.A.	Investigative	[14]
GSK1331268	DMIWY7Q	Discovery agent	N.A.	Investigative	[26]
JNJ-42153605	DMLOQ92	Discovery agent	N.A.	Investigative	[27]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[19]
LY-379268	DMME40U	Discovery agent	N.A.	Investigative	[28]
LY-389795	DM6Y2XG	Discovery agent	N.A.	Investigative	[28]
MGS0028	DMIMKFZ	Discovery agent	N.A.	Investigative	[29]
MNI-135	DMBJFH9	Discovery agent	N.A.	Investigative	[30]
MNI-136	DM5C9VI	Discovery agent	N.A.	Investigative	[30]
MNI-137	DMKRI1J	Discovery agent	N.A.	Investigative	[30]
PCCG-4	DMD9KYN	Discovery agent	N.A.	Investigative	[31]
PMID20409708C34	DMA2Y74	Discovery agent	N.A.	Investigative	[32]
PMID21155570C14	DM7I341	Discovery agent	N.A.	Investigative	[33]
PMID22364337C48	DMRLG7Z	Discovery agent	N.A.	Investigative	[34]
PTBE	DMY02IR	Discovery agent	N.A.	Investigative	[35]
Ro4491533	DMJLSX0	Discovery agent	N.A.	Investigative	[36]
RO4988546	DM6SQ9A	Discovery agent	N.A.	Investigative	[37]
RO5488608	DMHXGCO	Discovery agent	N.A.	Investigative	[37]
Ro64-5229	DMXOTHC	Discovery agent	N.A.	Investigative	[38]
THIIC	DM3KU46	Discovery agent	N.A.	Investigative	[39]
[3H]2,2,2-TEMPS	DMQO8AF	Discovery agent	N.A.	Investigative	[37]
[3H]JNJ-40068782	DMSE56B	Discovery agent	N.A.	Investigative	[40]
[3H]LY341495	DMGX0Y8	Discovery agent	N.A.	Investigative	[19]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[41]

References

• [1] Pharmacokinetic and pharmacodynamic characterisation of JNJ-40411813, a positive allosteric modulator of mGluR2, in two randomised, double-blind phase-I studies. J Psychopharmacol. 2015 Apr;29(4):414-25.
• [2] ClinicalTrials.gov (NCT03044249) A Study of MP-101 in Dementia-Related Psychosis and/or Agitation and Aggression. U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat. 2013; 9: 1101-1112.
• [5] MGlu2 receptor-mediated modulation of conditioned avoidance behavior in rats. European journal of pharmacology. 01/2014; 727(1).
• [6] 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.
• [7] Metabotropic glutamate receptor subtype 2 (GRM2; MGLUR2); GRM3 (MGLUR3). SciBX 3(13); doi:10.1038/scibx.2010.413. April 1 2010
• [8] 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.
• [9] Annual Reports in Medicinal Chemistry. Volume 47, 2012, Page(78).
• [10] 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.
• [11] 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.
• [12] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [13] Annual Reports in Medicinal Chemistry. Elsevier (ISBN: 9780123964922). 2012, p78
• [14] 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.
• [15] Clinical pipeline report, company report or official report of Roche.
• [16] Company report (Roche pipeline: 15 April 2014)
• [17] Metabotropic glutamate receptor subtype 2/3 (mGluR2/3); serotonin receptor (5-HT2A receptor). SciBX 1(6); doi:10.1038/scibx.2008.145. March 6 2008
• [18] Characterization of [3H]-(2S,2'R,3'R)-2-(2',3'-dicarboxy-cyclopropyl)glycine ([3H]-DCG IV) binding to metabotropic mGlu2 receptor-transfected cell membranes. Br J Pharmacol. 1998 Feb;123(3):497-504.
• [19] [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.
• [20] 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.
• [21] Metabotropic glutamate 2 receptor potentiators: receptor modulation, frequency-dependent synaptic activity, and efficacy in preclinical anxiety and... Psychopharmacology (Berl). 2005 Apr;179(1):271-83.
• [22] SAR study of a subtype selective allosteric potentiator of metabotropic glutamate 2 receptor, N-(4-phenoxyphenyl)-N-(3-pyridinylmethyl)ethanesulfonamide. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3099-102.
• [23] Biphenyl-indanones: allosteric potentiators of the metabotropic glutamate subtype 2 receptor. Bioorg Med Chem Lett. 2005 Oct 1;15(19):4354-8.
• [24] Attenuation of seizures induced by homocysteic acid in immature rats by metabotropic glutamate group II and group III receptor agonists. Brain Res. 2001 Jul 27;908(2):120-9.
• [25] 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: 290).
• [26] The identification of structurally novel, selective, orally bioavailable positive modulators of mGluR2. Bioorg Med Chem Lett. 2010 Jan 15;20(2):759-62.
• [27] Discovery of 3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): a positive allosteric modulator of the metabotropic glutamate 2 receptor. JMed Chem. 2012 Oct 25;55(20):8770-89.
• [28] Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of (-)-4-amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate: identif... J Med Chem. 2007 Jan 25;50(2):233-40.
• [29] Synthesis, SARs, and pharmacological characterization of 2-amino-3 or 6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent, selective, and orally active group II metabotropic glutamate receptor agonists. J Med Chem. 2000 Dec 14;43(25):4893-909.
• [30] A novel family of potent negative allosteric modulators of group II metabotropic glutamate receptors. J Pharmacol Exp Ther. 2007 Jul;322(1):254-64.
• [31] Synthesis and pharmacological characterization of all sixteen stereoisomers of 2-(2'-carboxy-3'-phenylcyclopropyl)glycine. Focus on (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, a novel and selective group II metabotropic glutamate receptors antagonist. J Med Chem. 1996 May 24;39(11):2259-69.
• [32] 3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: Hit-to-lead efforts. Bioorg Med Chem Lett. 2010 May 15;20(10):3129-33.
• [33] Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats. J Med Chem. 2011 Jan 13;54(1):342-53.
• [34] Discovery of 1,4-disubstituted 3-cyano-2-pyridones: a new class of positive allosteric modulators of the metabotropic glutamate 2 receptor. J Med Chem. 2012 Mar 8;55(5):2388-405.
• [35] Phenyl-tetrazolyl acetophenones: discovery of positive allosteric potentiatiors for the metabotropic glutamate 2 receptor. J Med Chem. 2004 Aug 26;47(18):4595-9.
• [36] Characterization of an mGluR2/3 negative allosteric modulator in rodent models of depression. J Neurogenet. 2011 Dec;25(4):152-66.
• [37] Structural determinants of allosteric antagonism at metabotropic glutamate receptor 2: mechanistic studies with new potent negative allosteric modulators. Br J Pharmacol. 2011 Sep;164(2b):521-37.
• [38] Synthesis of heterocyclic enol ethers and their use as group 2 metabotropic glutamate receptor antagonists. Bioorg Med Chem Lett. 1999 Aug 2;9(15):2173-6.
• [39] N-(4-((2-(trifluoromethyl)-3-hydroxy-4-(isobutyryl)phenoxy)methyl)benzyl)-1-methyl-1H-imidazole-4-carboxamide (THIIC), a novel metabotropic glutamate 2 potentiator with potential anxiolytic/antidepressant properties: in vivo profiling suggests a link between behavioral and central nervous system neurochemical changes. J Pharmacol Exp Ther. 2011 Jan;336(1):165-77.
• [40] Pharmacological characterization of JNJ-40068782, a new potent, selective, and systemically active positive allosteric modulator of the mGlu2 receptor and its radioligand [3H]JNJ-40068782. J Pharmacol Exp Ther. 2013 Sep;346(3):514-27.
• [41] 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.