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

General Information of Drug (ID: DMVQK4Y)

• Drug Name: 2-methyl-6-(phenylethynyl)pyridine Drug Info
• Synonyms: 2-Methyl-6-(phenylethynyl)pyridine; MPEP; 96206-92-7; 6-Methyl-2-(phenylethynyl)pyridine; 2-methyl-6-(2-phenylethynyl)pyridine; UNII-7VC0YVI27Y; 7VC0YVI27Y; CHEMBL66654; CHEBI:64159; Pyridine, 2-methyl-6-(phenylethynyl)-; Tocris-1212; AC1MHGB1; Lopac-M-5435; Lopac0_000738; MLS006011229; SCHEMBL103061; 2-Picoline, 6-phenylethynyl-; GTPL1426; DTXSID9043982; MolPort-003-958-770; HMS3651F13; 2-Methyl-6-phenylethynyl-pyridine; ZINC2581406; BCP05962; ZX-AN014840; 2-methyl-6-(phenylethynyl)-pyridine; s2809; HY-14609A; 2151AH

Indication

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

• Cross-matching ID:
  PubChem CID: 3025961
  ChEBI ID: CHEBI:64159
  CAS Number: CAS 96206-92-7
  TTD Drug ID: DMVQK4Y

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	[6]
AZD8529	DMEQ2N1	Schizophrenia	6A20	Discontinued in Phase 2	[7]
AZD-9272	DMYSBN3	Neuropathic pain	8E43.0	Discontinued in Phase 1	[8]
NPS-2390	DMMRY0Z	Cerebrovascular ischaemia	8B1Z	Preclinical	[9]
A-841720	DMSO8IE	Pain	MG30-MG3Z	Preclinical	[10]
LY-367385	DM98POQ	Neurological disorder	6B60	Terminated	[11]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[12]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[13]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[13]
(+)-MCPG	DMG5QJB	Discovery agent	N.A.	Investigative	[14]

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	[15]
ADX-48621	DM6GTMD	Parkinson disease	8A00.0	Phase 2/3	[16]
RG-7090	DMX8JYN	Fragile X syndrome	LD55	Phase 2	[17]
STX-107	DMLNKX7	Autism spectrum disorder	6A02	Phase 2	[18]
ADX10059	DMGVKHQ	Anxiety disorder	6B00-6B0Z	Phase 2	[19]
McN3377	DMTCADJ	Fragile X syndrome	LD55	Phase 1/2	[20]
MK-3328	DMW2O5D	Alzheimer disease	8A20	Phase 1	[21]
[3H]fenobam	DMBOXA1	Allodynia	MB40.1	Phase 1	[22]
RG7342	DMIW5NG	Schizophrenia	6A20	Phase 1	[23]
Tetra-hydro-oxazolopyridine derivative 2	DMP65Z4	N. A.	N. A.	Patented	[24]

Drug(s) Targeting Metabotropic glutamate receptor 4 (mGluR4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DT-1687	DMU2GP4	Parkinson disease	8A00.0	Phase 2	[25]
L-serine-O-phosphate	DMTJ1NH	Discovery agent	N.A.	Investigative	[26]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[27]
MAP4	DMUCE93	Discovery agent	N.A.	Investigative	[28]
MPPG	DMJHQ9T	Discovery agent	N.A.	Investigative	[28]
L-AP4	DMPJFGI	Discovery agent	N.A.	Investigative	[28]
PHCCC	DMNJY79	Discovery agent	N.A.	Investigative	[29]
LSP4-2022	DMBWHGP	Discovery agent	N.A.	Investigative	[30]
(S)-3,4-DCPG	DMG5BUA	Discovery agent	N.A.	Investigative	[31]
ACPT-I	DM264XN	Discovery agent	N.A.	Investigative	[32]

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	Inhibitor	[3]
Metabotropic glutamate receptor 4 (mGluR4)	TTICZ1O	GRM4_HUMAN	Modulator (allosteric modulator)	[4]
Metabotropic glutamate receptor 5 (mGluR5)	TTHS256	GRM5_HUMAN	Inhibitor	[5] , [2]

References

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• [2] Discovery and SAR of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of mGlu5. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6623-6.
• [3] Carbamoyloximes as novel non-competitive mGlu5 receptor antagonists. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4371-5.
• [4] Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP. Br J Pharmacol. 2003 Mar;138(6):1026-30.
• [5] 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology. 1999 Oct;38(10):1493-503.
• [6] Pfizer. Product Development Pipeline. March 31 2009.
• [7] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [8] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [9] Positive and negative modulation of group I metabotropic glutamate receptors. J Med Chem. 2008 Feb 14;51(3):634-47.
• [10] Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition. Behav Pharmacol. 2007 Jul;18(4):273-81.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] [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.
• [15] 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.
• [16] Pipeline of Addex Pharma. Addex Pharma. 2009.
• [17] The challenges of clinical trials in fragile X syndrome. Psychopharmacology (Berl) 2014; 231(6): 1237-1250.
• [18] 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.
• [19] 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.
• [20] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [21] 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).
• [22] 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.
• [23] Clinical pipeline report, company report or official report of Roche.
• [24] mGlu5 negative allosteric modulators: a patent review (2013 - 2016).Expert Opin Ther Pat. 2017 Jun;27(6):691-706.
• [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: 292).
• [26] Serine-O-phosphate has affinity for type IV, but not type I, metabotropic glutamate receptor. Neuroreport. 1993 Sep;4(9):1099-101.
• [27] Agonist analysis of 2-(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells. Br J Pharmacol. 1992 Oct;107(2):539-43.
• [28] Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor. J Biol Chem. 1999 Apr 9;274(15):10008-13.
• [29] (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection. Neuropharmacology. 2003 Dec;45(7):895-906.
• [30] 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.
• [31] (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.
• [32] Synthesis and pharmacological characterization of aminocyclopentanetricarboxylic acids: new tools to discriminate between metabotropic glutamate receptor subtypes. J Med Chem. 1997 Sep 12;40(19):3119-29.