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

General Information of Drug (ID: DMQK4I2)

• Drug Name: (S)-4C3HPG Drug Info
• Synonyms: (S)-4-CARBOXY-3-HYDROXYPHENYLGLYCINE; 85148-82-9; (s)-4C3HPG; DFS3SIU1ME; UNII-DFS3SIU1ME; (S)-4-(amino(carboxy)methyl)-2-hydroxybenzoic acid; CHEMBL39372; (S)-4C3H-PG; Benzeneacetic acid, alpha-amino-4-carboxy-3-hydroxy-, (alphaS)-; 4-[(1S)-1-amino-2-hydroxy-2-oxoethyl]-2-hydroxybenzoic acid; 4C3HPG; Tocris-0320; 4-Carboxy-3-hydroxyphenylglycine, (S)-; AC1NSKO9; GTPL1374; SCHEMBL12648356; CTK8F2145; MolPort-003-983-491; ZINC2559031; PDSP1_001316; PDSP2_001300; BDBM50053585; 4-Carboxy-3-hydroxy-L-phenylglycine; BN0022

Indication

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

• Cross-matching ID:
  PubChem CID: 5311455
  CAS Number: CAS 85148-82-9
  TTD Drug ID: DMQK4I2

Molecule-Related Drug Atlas

Drug(s) Targeting Metabotropic glutamate receptor 1 (mGluR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-1913539	DMXEU14	Alzheimer disease	8A20	Discontinued in Phase 3	[4]
AZD8529	DMEQ2N1	Schizophrenia	6A20	Discontinued in Phase 2	[5]
AZD-9272	DMYSBN3	Neuropathic pain	8E43.0	Discontinued in Phase 1	[6]
NPS-2390	DMMRY0Z	Cerebrovascular ischaemia	8B1Z	Preclinical	[7]
A-841720	DMSO8IE	Pain	MG30-MG3Z	Preclinical	[8]
LY-367385	DM98POQ	Neurological disorder	6B60	Terminated	[9]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[10]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[2]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[2]
(+)-MCPG	DMG5QJB	Discovery agent	N.A.	Investigative	[11]

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	[12]
Oleoyl-estrone	DM0RA8F	Alzheimer disease	8A20	Phase 2	[13]
MP-101	DMYCITZ	Alzheimer disease	8A20	Phase 2	[14]
JNJ-64281802	DMNMSVX	Dengue	1D20-1D2Z	Phase 2	[15]
BCI-838	DMRXDN3	Major depressive disorder	6A70.3	Phase 1	[16]
Pomaglumetad	DMTOLI5	Schizophrenia	6A20	Phase 1	[17]
BCI-632	DMZYCWT	Alzheimer disease	8A20	Phase 1	[18]
LY-2979165	DM16IX2	Bipolar disorder	6A60	Phase 1	[19]
JNJ-42491293	DMOL9JR	Psychiatric disorder	6E8Z	Phase 1	[20]
ADX71149	DMBUOX4	Epilepsy	8A60-8A68	Phase 1	[21]

Drug(s) Targeting Metabotropic glutamate receptor 5 (mGluR5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AFQ056	DMMHSLC	Fragile X syndrome	LD55	Phase 2/3	[22]
ADX-48621	DM6GTMD	Parkinson disease	8A00.0	Phase 2/3	[23]
RG-7090	DMX8JYN	Fragile X syndrome	LD55	Phase 2	[24]
STX-107	DMLNKX7	Autism spectrum disorder	6A02	Phase 2	[25]
ADX10059	DMGVKHQ	Anxiety disorder	6B00-6B0Z	Phase 2	[26]
McN3377	DMTCADJ	Fragile X syndrome	LD55	Phase 1/2	[27]
MK-3328	DMW2O5D	Alzheimer disease	8A20	Phase 1	[28]
[3H]fenobam	DMBOXA1	Allodynia	MB40.1	Phase 1	[29]
RG7342	DMIW5NG	Schizophrenia	6A20	Phase 1	[30]
BMS-984923	DMFNDUL	Alzheimer disease	8A20	Phase 1	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Metabotropic glutamate receptor 1 (mGluR1)	TTVBPDM	GRM1_HUMAN	Antagonist	[2]
Metabotropic glutamate receptor 2 (mGluR2)	TTXJ47W	GRM2_HUMAN	Agonist	[3]
Metabotropic glutamate receptor 5 (mGluR5)	TTHS256	GRM5_HUMAN	Antagonist	[2]

References

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• [2] Characterization of [(3)H]Quisqualate binding to recombinant rat metabotropic glutamate 1a and 5a receptors and to rat and human brain sections. J Neurochem. 2000 Dec;75(6):2590-601.
• [3] 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.
• [4] Pfizer. Product Development Pipeline. March 31 2009.
• [5] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [6] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [7] Positive and negative modulation of group I metabotropic glutamate receptors. J Med Chem. 2008 Feb 14;51(3):634-47.
• [8] Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition. Behav Pharmacol. 2007 Jul;18(4):273-81.
• [9] Anticonvulsant actions of LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid). Eur J Pharmacol. 1999 Feb 26;368(1):17-24.
• [10] Mutational analysis and molecular modeling of the allosteric binding site of a novel, selective, noncompetitive antagonist of the metabotropic glut... J Biol Chem. 2003 Mar 7;278(10):8340-7.
• [11] [3H]R214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists. Mol Pharmacol. 2003 May;63(5):1082-93.
• [12] Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat. 2013; 9: 1101-1112.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] ClinicalTrials.gov (NCT03044249) A Study of MP-101 in Dementia-Related Psychosis and/or Agitation and Aggression. U.S. National Institutes of Health.
• [15] 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.
• [16] Metabotropic glutamate receptor subtype 2 (GRM2; MGLUR2); GRM3 (MGLUR3). SciBX 3(13); doi:10.1038/scibx.2010.413. April 1 2010
• [17] 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.
• [18] 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.
• [19] Annual Reports in Medicinal Chemistry. Volume 47, 2012, Page(78).
• [20] 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.
• [21] MGlu2 receptor-mediated modulation of conditioned avoidance behavior in rats. European journal of pharmacology. 01/2014; 727(1).
• [22] Metabolism and disposition of the metabotropic glutamate receptor 5 antagonist (mGluR5) mavoglurant (AFQ056) in healthy subjects. Drug Metab Dispos. 2013 Sep;41(9):1626-41.
• [23] Pipeline of Addex Pharma. Addex Pharma. 2009.
• [24] The challenges of clinical trials in fragile X syndrome. Psychopharmacology (Berl) 2014; 231(6): 1237-1250.
• [25] Social Communication is an Emerging Target for Pharmacotherapy in Autism Spectrum Disorder - A Review of the Literature on Potential Agents. J Can Acad Child Adolesc Psychiatry. 2014 February; 23(1):20-30.
• [26] A proof-of-concept study evaluating the effect of ADX10059, a metabotropic glutamate receptor-5 negative allosteric modulator, on acid exposure and... Gut. 2009 Sep;58(9):1192-9.
• [27] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [28] 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: 293).
• [29] Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agon... J Pharmacol Exp Ther. 2005 Nov;315(2):711-21.
• [30] Clinical pipeline report, company report or official report of Roche.
• [31] Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer's Mouse Phenotypes. Cell Rep. 2017 Jul 5;20(1):76-88.