Details of the Drug

General Information of Drug (ID: DM3KU46)

• Drug Name: THIIC
• Synonyms: THIIC; SCHEMBL1828988; GTPL6259; RYINQFMHVVYWNS-UHFFFAOYSA-N; N-({4-[3-hydroxy-4-(2-methylpropanoyl)-2-(trifluoromethyl)phenoxymethyl]phenyl}methyl)-1-methyl-1H-imidazole-4-carboxamide; 1-Methyl-1H-imidazole-4-carboxylic acid 4-(3-hydroxy-4-isobutyryl-2-trifluoromethyl-phenoxymethyl)-benzylamide; N-(4-{[3-hydroxy-4-(2-methylpropanoyl)-2-(trifluoromethyl)phenoxy]methyl}benzyl)-1-methyl-1 h-imidazole-4-carboxamide

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 475.5
  Topological Polar Surface Area (xlogp); 4.4
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C24H24F3N3O4
  IUPAC Name: N-[[4-[[3-hydroxy-4-(2-methylpropanoyl)-2-(trifluoromethyl)phenoxy]methyl]phenyl]methyl]-1-methylimidazole-4-carboxamide
  Canonical SMILES: CC(C)C(=O)C1=C(C(=C(C=C1)OCC2=CC=C(C=C2)CNC(=O)C3=CN(C=N3)C)C(F)(F)F)O
  InChI: InChI=1S/C24H24F3N3O4/c1-14(2)21(31)17-8-9-19(20(22(17)32)24(25,26)27)34-12-16-6-4-15(5-7-16)10-28-23(33)18-11-30(3)13-29-18/h4-9,11,13-14,32H,10,12H2,1-3H3,(H,28,33)
  InChIKey: RYINQFMHVVYWNS-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 44595851
  TTD ID: D0I6WA

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	Modulator (allosteric modulator)	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Metabotropic glutamate receptor 2 (mGluR2)	DTT	GRM2	1.09E-01	-0.11	-0.2
Metabotropic glutamate receptor 2 (mGluR2)	DTT	GRM2	3.19E-01	-0.06	-0.34

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: 6259).
• [2] 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.
• [3] Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat. 2013; 9: 1101-1112.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] ClinicalTrials.gov (NCT03044249) A Study of MP-101 in Dementia-Related Psychosis and/or Agitation and Aggression. U.S. National Institutes of Health.
• [6] Metabotropic glutamate receptor subtype 2 (GRM2; MGLUR2); GRM3 (MGLUR3). SciBX 3(13); doi:10.1038/scibx.2010.413. April 1 2010
• [7] 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.
• [8] 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.
• [9] Annual Reports in Medicinal Chemistry. Volume 47, 2012, Page(78).
• [10] 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.
• [11] MGlu2 receptor-mediated modulation of conditioned avoidance behavior in rats. European journal of pharmacology. 01/2014; 727(1).
• [12] 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.