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

General Information of Drug (ID: DMNJY79)

• Drug Name: PHCCC Drug Info
• Synonyms: (-) PHCCC

Indication

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

• Cross-matching ID:
  PubChem CID: 5866327
  ChEBI ID: CHEBI:91731
  TTD Drug ID: DMNJY79

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	[5]
AZD8529	DMEQ2N1	Schizophrenia	6A20	Discontinued in Phase 2	[6]
AZD-9272	DMYSBN3	Neuropathic pain	8E43.0	Discontinued in Phase 1	[7]
NPS-2390	DMMRY0Z	Cerebrovascular ischaemia	8B1Z	Preclinical	[8]
A-841720	DMSO8IE	Pain	MG30-MG3Z	Preclinical	[9]
LY-367385	DM98POQ	Neurological disorder	6B60	Terminated	[10]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[11]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[12]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[12]
(+)-MCPG	DMG5QJB	Discovery agent	N.A.	Investigative	[13]

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	[14]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[15]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[16]
MAP4	DMUCE93	Discovery agent	N.A.	Investigative	[17]
MPPG	DMJHQ9T	Discovery agent	N.A.	Investigative	[16]
[3H]LY341495	DMGX0Y8	Discovery agent	N.A.	Investigative	[18]
alpha-methylserine-O-phosphate	DMCIH1X	Discovery agent	N.A.	Investigative	[17]
L-AP4	DMPJFGI	Discovery agent	N.A.	Investigative	[14]
LSP4-2022	DMBWHGP	Discovery agent	N.A.	Investigative	[19]
(S)-3,4-DCPG	DMG5BUA	Discovery agent	N.A.	Investigative	[20]

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	[21]
L-serine-O-phosphate	DMTJ1NH	Discovery agent	N.A.	Investigative	[22]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[23]
MAP4	DMUCE93	Discovery agent	N.A.	Investigative	[24]
MPPG	DMJHQ9T	Discovery agent	N.A.	Investigative	[24]
L-AP4	DMPJFGI	Discovery agent	N.A.	Investigative	[24]
2-methyl-6-(phenylethynyl)pyridine	DMVQK4Y	Discovery agent	N.A.	Investigative	[25]
LSP4-2022	DMBWHGP	Discovery agent	N.A.	Investigative	[19]
(S)-3,4-DCPG	DMG5BUA	Discovery agent	N.A.	Investigative	[20]
ACPT-I	DM264XN	Discovery agent	N.A.	Investigative	[26]

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	Modulator (allosteric modulator)	[2]
Metabotropic glutamate receptor 4 (mGluR4)	TTICZ1O	GRM4_HUMAN	Modulator (allosteric modulator)	[3]
Metabotropic glutamate receptor 6 (mGluR6)	TTWRP2F	GRM6_HUMAN	Modulator (allosteric modulator)	[4]

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: 1416).
• [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. (Target id: 289).
• [3] (-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection. Neuropharmacology. 2003 Dec;45(7):895-906.
• [4] 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.
• [5] Pfizer. Product Development Pipeline. March 31 2009.
• [6] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [7] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [8] Positive and negative modulation of group I metabotropic glutamate receptors. J Med Chem. 2008 Feb 14;51(3):634-47.
• [9] Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition. Behav Pharmacol. 2007 Jul;18(4):273-81.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] [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.
• [14] Cloning, distribution and functional expression of the human mGlu6 metabotropic glutamate receptor. Neuropharmacology. 1997 Feb;36(2):145-52.
• [15] 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.
• [16] 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).
• [17] The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr Drug Targets CNS Neurol Disord. 2002 Jun;1(3):297-317.
• [18] 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.
• [19] 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.
• [20] (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.
• [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: 292).
• [22] Serine-O-phosphate has affinity for type IV, but not type I, metabotropic glutamate receptor. Neuroreport. 1993 Sep;4(9):1099-101.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] 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.