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

General Information of Drug (ID: DMCIH1X)

• Drug Name: alpha-methylserine-O-phosphate Drug Info
• Synonyms: alpha-MSOP

Indication

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

• Cross-matching ID:
  PubChem CID: 3964633
  CAS Number: CAS 66515-29-5
  TTD Drug ID: DMCIH1X

Molecule-Related Drug Atlas

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	[5]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[6]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[7]
MAP4	DMUCE93	Discovery agent	N.A.	Investigative	[3]
MPPG	DMJHQ9T	Discovery agent	N.A.	Investigative	[7]
[3H]LY341495	DMGX0Y8	Discovery agent	N.A.	Investigative	[4]
L-AP4	DMPJFGI	Discovery agent	N.A.	Investigative	[5]
PHCCC	DMNJY79	Discovery agent	N.A.	Investigative	[8]
LSP4-2022	DMBWHGP	Discovery agent	N.A.	Investigative	[9]
(S)-3,4-DCPG	DMG5BUA	Discovery agent	N.A.	Investigative	[10]

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	[4]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[11]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[4]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[4]
(+)-MCPG	DMG5QJB	Discovery agent	N.A.	Investigative	[4]
MAP4	DMUCE93	Discovery agent	N.A.	Investigative	[4]
MPPG	DMJHQ9T	Discovery agent	N.A.	Investigative	[4]
[3H]LY341495	DMGX0Y8	Discovery agent	N.A.	Investigative	[4]
L-AP4	DMPJFGI	Discovery agent	N.A.	Investigative	[4]
LSP4-2022	DMBWHGP	Discovery agent	N.A.	Investigative	[9]

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 8 (mGluR8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-serine-O-phosphate	DMTJ1NH	Discovery agent	N.A.	Investigative	[22]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[11]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[22]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[23]
MAP4	DMUCE93	Discovery agent	N.A.	Investigative	[24]
MPPG	DMJHQ9T	Discovery agent	N.A.	Investigative	[23]
L-AP4	DMPJFGI	Discovery agent	N.A.	Investigative	[22]
(S)-3,4-DCPG	DMG5BUA	Discovery agent	N.A.	Investigative	[10]
ACPT-I	DM264XN	Discovery agent	N.A.	Investigative	[25]
CPPG	DMVHX5T	Discovery agent	N.A.	Investigative	[24]

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	[2]
Metabotropic glutamate receptor 6 (mGluR6)	TTWRP2F	GRM6_HUMAN	Antagonist	[3]
Metabotropic glutamate receptor 7 (mGluR7)	TT0I76D	GRM7_HUMAN	Antagonist	[4]
Metabotropic glutamate receptor 8 (mGluR8)	TT0IFKL	GRM8_HUMAN	Antagonist	[3]

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: 1398).
• [2] 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.
• [3] The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr Drug Targets CNS Neurol Disord. 2002 Jun;1(3):297-317.
• [4] 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.
• [5] Cloning, distribution and functional expression of the human mGlu6 metabotropic glutamate receptor. Neuropharmacology. 1997 Feb;36(2):145-52.
• [6] 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.
• [7] 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).
• [8] 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.
• [9] 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.
• [10] (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.
• [11] 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.
• [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] Cloning and functional expression of alternative spliced variants of the human metabotropic glutamate receptor 8. Brain Res Mol Brain Res. 1999 Apr 20;67(2):201-10.
• [23] Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells. Brain Res Mol Brain Res. 1998 Jan;53(1-2):88-97.
• [24] Constraints on proper folding of the amino terminal domains of group III metabotropic glutamate receptors. Brain Res Mol Brain Res. 2000 Mar 10;76(1):180-90.
• [25] Pharmacological characterization of the rat metabotropic glutamate receptor type 8a revealed strong similarities and slight differences with the type 4a receptor. Eur J Pharmacol. 2000 Apr 7;394(1):17-26.