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

General Information of Drug (ID: DMTS1X5)

• Drug Name: LY-2300559 Drug Info
• Synonyms: MGlu2 Pot/Cys (migraine prevention), Eli Lilly; Metabotropic glutamate 2 receptor potentiator/cysteinyl leukotriene receptor 1 antagonist (migraine), Eli Lilly; Mglu2 potentiator/CysLT1 antagonist (migraine prevention), Eli Lilly

Indication

Disease Entry	ICD 11	Status	REF
Migraine	8A80	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 11611800
  CAS Number: CAS 889116-06-7
  TTD Drug ID: DMTS1X5

Molecule-Related Drug Atlas

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	[3]
Oleoyl-estrone	DM0RA8F	Alzheimer disease	8A20	Phase 2	[4]
MP-101	DMYCITZ	Alzheimer disease	8A20	Phase 2	[5]
JNJ-64281802	DMNMSVX	Dengue	1D20-1D2Z	Phase 2	[6]
BCI-838	DMRXDN3	Major depressive disorder	6A70.3	Phase 1	[7]
Pomaglumetad	DMTOLI5	Schizophrenia	6A20	Phase 1	[8]
BCI-632	DMZYCWT	Alzheimer disease	8A20	Phase 1	[9]
LY-2979165	DM16IX2	Bipolar disorder	6A60	Phase 1	[10]
JNJ-42491293	DMOL9JR	Psychiatric disorder	6E8Z	Phase 1	[11]
ADX71149	DMBUOX4	Epilepsy	8A60-8A68	Phase 1	[12]

Drug(s) Targeting Leukotriene CysLT1 receptor (CYSLTR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Montelukast	DMD157S	Allergic asthma	CA23.0	Approved	[13]
Zafirlukast	DMHNQOG	Asthma	CA23	Approved	[14]
Pranlukast	DMYHDCA	Allergic rhinitis	CA08.0	Approved	[15]
Cinalukast	DMFIC0M	Asthma	CA23	Approved	[16]
KP-496	DMCO8UZ	Asthma	CA23	Phase 2	[17]
BAY-X-7195	DM2XE80	Asthma	CA23	Phase 2	[18]
Masilukast	DMDTI0L	Asthma	CA23	Phase 2	[19]
LM-1507.NA	DMW6VA0	Asthma	CA23	Phase 2	[20]
Iralukast	DMQ3RWN	Asthma	CA23	Phase 2	[21]
YM-57158	DMS31YW	Allergic rhinitis	CA08.0	Phase 1	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Leukotriene CysLT1 receptor (CYSLTR1)	TTGKOY9	CLTR1_HUMAN	Modulator	[2]
Metabotropic glutamate receptor 2 (mGluR2)	TTXJ47W	GRM2_HUMAN	Modulator	[2]

References

• [1] ClinicalTrials.gov (NCT01184508) A Study in Migraine Prevention. U.S. National Institutes of Health.
• [2] Annual Reports in Medicinal Chemistry. Elsevier (ISBN: 9780123964922). 2012, p78
• [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] 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.
• [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] 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).
• [13] Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats. J Surg Res. 2010 Mar;159(1):588-94.
• [14] Inhibitory effects of zafirlukast on respiratory bursts of human neutrophils. Drugs Exp Clin Res. 2002;28(4):133-45.
• [15] Beneficial effects of leukotriene receptor antagonists in the prevention of cedar pollinosis in a community setting. J Investig Allergol Clin Immunol. 2009;19(3):195-203.
• [16] Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D4-receptor antagonist cinalukast. J Allergy Clin Immunol. 1997 Feb;99(2):210-5.
• [17] Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Allergol Int. 2006 Dec;55(4):403-10.
• [18] The effect of a novel leukotriene C4/D4 antagonist, BAY-x-7195, on experimental allergic reactions. Prostaglandins. 1995 Nov-Dec;50(5-6):269-85.
• [19] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [20] Pharmacological differences among CysLT(1) receptor antagonists with respect to LTC(4) and LTD(4) in human lung parenchyma. Biochem Pharmacol. 2002 Apr 15;63(8):1537-46.
• [21] Pharmacological characterization of the cysteinyl-leukotriene antagonists CGP 45715A (iralukast) and CGP 57698 in human airways in vitro. Br J Pharmacol. 1998 Feb;123(3):590-8.
• [22] In vitro pharmacologic profile of YM158, a new dual antagonist for LTD4 and TXA2 receptors. J Pharmacol Exp Ther. 1998 Nov;287(2):633-9.