Details of the Drug

General Information of Drug (ID: DMSC4K1)

• Drug Name: LY-544344

Indication

Disease Entry	ICD 11	Status	REF
Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[1]

• Therapeutic Class: Psychiatric
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 256.25
  Topological Polar Surface Area (xlogp); -3.5
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 6
• Chemical Identifiers:
  Formula: C11H16N2O5
  IUPAC Name: (1S,2S,5R,6S)-2-[[(2S)-2-aminopropanoyl]amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid
  Canonical SMILES: C[C@@H](C(=O)N[C@]1(CC[C@@H]2[C@H]1[C@H]2C(=O)O)C(=O)O)N
  InChI: InChI=1S/C11H16N2O5/c1-4(12)8(14)13-11(10(17)18)3-2-5-6(7(5)11)9(15)16/h4-7H,2-3,12H2,1H3,(H,13,14)(H,15,16)(H,17,18)/t4-,5-,6-,7-,11-/m0/s1
  InChIKey: UPSXYNJDCKOCFD-QIMCWZKGSA-N
• Cross-matching ID:
  PubChem CID: 9857256
  CAS Number: 441765-98-6
  TTD ID: D0P4BQ

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

Molecular Expression Atlas of This Drug

• The Studied Disease: Anxiety disorder
• ICD Disease Classification: 6B00-6B0Z

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] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018821)
• [2] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [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] Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat. 2013; 9: 1101-1112.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] ClinicalTrials.gov (NCT03044249) A Study of MP-101 in Dementia-Related Psychosis and/or Agitation and Aggression. U.S. National Institutes of Health.
• [7] Metabotropic glutamate receptor subtype 2 (GRM2; MGLUR2); GRM3 (MGLUR3). SciBX 3(13); doi:10.1038/scibx.2010.413. April 1 2010
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Annual Reports in Medicinal Chemistry. Volume 47, 2012, Page(78).
• [12] 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.
• [13] MGlu2 receptor-mediated modulation of conditioned avoidance behavior in rats. European journal of pharmacology. 01/2014; 727(1).