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

General Information of Drug (ID: DMMRY0Z)

• Drug Name: NPS-2390 Drug Info
• Synonyms: N-(Adamantan-1-yl)quinoxaline-2-carboxamide; NPS 2390; 226878-01-9; NPS2390; N-(1-adamantyl)quinoxaline-2-carboxamide; CHEMBL399160; N-(adamantan-1-yl)quinoxaline-2-carboxamide; quinoxaline-2-carboxylic acid adamantan-1-ylamide; N-tricyclo[33113,7]dec-1-yl-2-quinoxalinecarboxamide; AC1OF2ZL; SCHEMBL659603; GTPL1384; NPS-239; DTXSID10427729; MolPort-003-351-281; ZKFVOZCCAXQXBU-UHFFFAOYSA-N; ZINC3966256; PDSP2_001301; BDBM50231744; PDSP1_001317; AKOS001304198; NPS-2390 solution, 30 mM in DMSO; N-(1-Adamantyl)-2-quinoxalinecarboxamide; Quinoxaline-2-carboxylic acid adamantan-1-ylamide

Indication

Disease Entry	ICD 11	Status	REF
Cerebrovascular ischaemia	8B1Z	Preclinical	[1] , [2]

• Cross-matching ID:
  PubChem CID: 7067728
  CAS Number: CAS 226878-01-9
  TTD Drug ID: DMMRY0Z

Molecule-Related Drug Atlas

Drug(s) Targeting Metabotropic glutamate receptor 1 (mGluR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-1913539	DMXEU14	Alzheimer disease	8A20	Discontinued in Phase 3	[5]
AZD8529	DMEQ2N1	Schizophrenia	6A20	Discontinued in Phase 2	[6]
AZD-9272	DMYSBN3	Neuropathic pain	8E43.0	Discontinued in Phase 1	[7]
A-841720	DMSO8IE	Pain	MG30-MG3Z	Preclinical	[8]
LY-367385	DM98POQ	Neurological disorder	6B60	Terminated	[9]
[3H]quisqualate	DMDQBTX	Discovery agent	N.A.	Investigative	[10]
L-CCG-I	DMPZ8XH	Discovery agent	N.A.	Investigative	[11]
(1S,3R)-ACPD	DM5DOAF	Discovery agent	N.A.	Investigative	[11]
(+)-MCPG	DMG5QJB	Discovery agent	N.A.	Investigative	[12]
PHCCC	DMNJY79	Discovery agent	N.A.	Investigative	[13]

Drug(s) Targeting Extracellular calcium-sensing receptor (CASR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cinacalcet	DMCX0K3	Hyperparathyroidism	5A51	Approved	[14]
Etelcalcetide	DMHP9BL	Secondary hyperparathyroidism	5A51.1	Approved	[15]
ASP7991	DM3TN1A	Hyperparathyroidism	5A51	Phase 2	[16]
MK-5442	DMHTIGU	Osteoporosis	FB83.0	Phase 2	[17]
ATF-936	DMWGKHZ	Osteoporosis	FB83.0	Phase 1	[18]
AXT-914	DM7ZU3B	Osteoporosis	FB83.0	Phase 1	[19]
R-568	DM5NWPD	N. A.	N. A.	Discontinued in Phase 2	[20]
Ronacaleret	DM10ZJP	Osteoporosis	FB83.0	Discontinued in Phase 2	[21]
NPS-2143	DMQPXLF	Osteoporosis	FB83.0	Discontinued in Phase 2	[22]
calindol	DMY9P6E	Discovery agent	N.A.	Investigative	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Extracellular calcium-sensing receptor (CASR)	TTBUYHA	CASR_HUMAN	Modulator	[3]
Metabotropic glutamate receptor 1 (mGluR1)	TTVBPDM	GRM1_HUMAN	Inhibitor	[4]

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: 1384).
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014988)
• [3] The Extracellular Calcium-Sensing Receptor (CASR) Regulates Gonadotropins-Induced Meiotic Maturation of Porcine Oocytes.Biol Reprod.2015 Dec;93(6):131.
• [4] Positive and negative modulation of group I metabotropic glutamate receptors. J Med Chem. 2008 Feb 14;51(3):634-47.
• [5] Pfizer. Product Development Pipeline. March 31 2009.
• [6] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [7] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [8] Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition. Behav Pharmacol. 2007 Jul;18(4):273-81.
• [9] Anticonvulsant actions of LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid). Eur J Pharmacol. 1999 Feb 26;368(1):17-24.
• [10] Mutational analysis and molecular modeling of the allosteric binding site of a novel, selective, noncompetitive antagonist of the metabotropic glut... J Biol Chem. 2003 Mar 7;278(10):8340-7.
• [11] Characterization of [(3)H]Quisqualate binding to recombinant rat metabotropic glutamate 1a and 5a receptors and to rat and human brain sections. J Neurochem. 2000 Dec;75(6):2590-601.
• [12] [3H]R214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists. Mol Pharmacol. 2003 May;63(5):1082-93.
• [13] 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: 289).
• [14] Clinical pipeline report, company report or official report of Amgen (2009).
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [16] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035616)
• [17] Antagonist for calcium-sensing receptor. JTT-305/MK-5442. Clin Calcium. 2011 Jan;21(1):89-93.
• [18] ATF936, a novel oral calcilytic, increases bone mineral density in rats and transiently releases parathyroid hormone in humans. Bone. 2011 Aug;49(2):233-41.
• [19] AXT914 a novel, orally-active parathyroid hormone-releasing drug in two early studies of healthy volunteers and postmenopausal women. Bone. 2014 Jul;64:204-10.
• [20] Mixed-effects modeling of the pharmacodynamic response to the calcimimetic agent R-568. Clin Pharmacol Ther. 1999 Jan;65(1):40-9.
• [21] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [22] Calcium-sensing receptor antagonist (calcilytic) NPS 2143 specifically blocks the increased secretion of endogenous Abeta42 prompted by exogenous fibrillary or soluble Abeta25-35 in human cortical astrocytes and neurons-therapeutic relevance to Alzheimer's disease. Biochim Biophys Acta. 2013 Oct;1832(10):1634-52.
• [23] N2-benzyl-N1-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamines and conformationally restrained indole analogues: development of calindol as a new calcimimetic acting at the calcium sensing receptor.Bioorg Med Chem Lett. 2004 Jun 21;14(12):3345-9.