Details of the Drug

General Information of Drug (ID: DMNTC7O)

• Drug Name: RO-4995819

Indication

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Phase 2	[1]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 447.3
  Topological Polar Surface Area (xlogp); 4.4
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 10
• Chemical Identifiers:
  Formula: C21H11F6N5
  IUPAC Name: 5-[2-[7-(trifluoromethyl)-5-[4-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]ethynyl]pyridin-2-amine
  Canonical SMILES: C1=CC(=CC=C1C2=NC3=C(C=NN3C(=C2)C(F)(F)F)C#CC4=CN=C(C=C4)N)C(F)(F)F
  InChI: InChI=1S/C21H11F6N5/c22-20(23,24)15-6-4-13(5-7-15)16-9-17(21(25,26)27)32-19(31-16)14(11-30-32)3-1-12-2-8-18(28)29-10-12/h2,4-11H,(H2,28,29)
  InChIKey: DMJHZVARRXJSEG-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 71533696
  CAS Number: 911115-16-7
  DrugBank ID: DB11923
  TTD ID: D08OTE

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	[2]
Metabotropic glutamate receptor 3 (mGluR3)	TT8A9EF	GRM3_HUMAN	Modulator	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Major depressive disorder
• ICD Disease Classification: 6A70.3

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
Metabotropic glutamate receptor 3 (mGluR3)	DTT	GRM3	6.89E-02	-0.39	-0.17
Metabotropic glutamate receptor 3 (mGluR3)	DTT	GRM3	4.60E-02	-0.05	-0.15

References

• [1] ClinicalTrials.gov (NCT01457677) ARTDeCo Study: A Study of RO4995819 in Patients With Major Depressive Disorder And Inadequate Response to Ongoing Antidepressant Treatment in Hoffmann-La Roche.
• [2] Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat. 2013; 9: 1101-1112.
• [3] Positive allosteric modulators of the metabotropic glutamate receptor 2 for the treatment of schizophrenia. Expert Opin Ther Pat. 2009 Sep;19(9):1259-75.
• [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] 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.
• [10] Annual Reports in Medicinal Chemistry. Volume 47, 2012, Page(78).
• [11] 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.
• [12] MGlu2 receptor-mediated modulation of conditioned avoidance behavior in rats. European journal of pharmacology. 01/2014; 727(1).