Details of the Drug

General Information of Drug (ID: DMQPXLF)

• Drug Name: NPS-2143
• Synonyms: NPS-2143; 284035-33-2; NPS 2143; NPS2143; UNII-Z25PJ77W7V; SB-262470; Z25PJ77W7V; CHEMBL180672; 2-CHLORO-6-[(2R)-3-[[1,1-DIMETHYL-2-(2-NAPHTHALENYL)ETHYL]AMINO]-2-HYDROXYPROPOXY]BENZONITRILE; C24H25ClN2O2; 2-chloro-6-[(2R)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]benzonitrile; (R)-2-chloro-6-(2-hydroxy-3-((2-methyl-1-(naphthalen-2-yl)propan-2-yl)amino)propoxy)benzonitrile; SB-262470A; (+)-NPS-2143; AC1OCFG2; GTPL716; SCHEMBL13597018; EX-A017; DTXSID10426075; MolPort-021-805-006; BCPP000077; ZINC3975668

Indication

Disease Entry	ICD 11	Status	REF
Osteoporosis	FB83.0	Discontinued in Phase 2	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 408.9
  Topological Polar Surface Area (xlogp); 5
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C24H25ClN2O2
  IUPAC Name: 2-chloro-6-[(2R)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]benzonitrile
  Canonical SMILES: CC(C)(CC1=CC2=CC=CC=C2C=C1)NC[C@H](COC3=C(C(=CC=C3)Cl)C#N)O
  InChI: InChI=1S/C24H25ClN2O2/c1-24(2,13-17-10-11-18-6-3-4-7-19(18)12-17)27-15-20(28)16-29-23-9-5-8-22(25)21(23)14-26/h3-12,20,27-28H,13,15-16H2,1-2H3/t20-/m1/s1
  InChIKey: PZUJQWHTIRWCID-HXUWFJFHSA-N
• Cross-matching ID:
  PubChem CID: 6918446
  CAS Number: 284035-33-2
  DrugBank ID: DB05695
  TTD ID: D0G1RH

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	Antagonist	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Osteoporosis
• ICD Disease Classification: FB83.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Extracellular calcium-sensing receptor (CASR)	DTT	CASR	5.81E-02	-0.03	-0.19

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: 716).
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010915)
• [3] 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.
• [4] Clinical pipeline report, company report or official report of Amgen (2009).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035616)
• [7] Antagonist for calcium-sensing receptor. JTT-305/MK-5442. Clin Calcium. 2011 Jan;21(1):89-93.
• [8] 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.
• [9] 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.
• [10] Mixed-effects modeling of the pharmacodynamic response to the calcimimetic agent R-568. Clin Pharmacol Ther. 1999 Jan;65(1):40-9.
• [11] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [12] The Extracellular Calcium-Sensing Receptor (CASR) Regulates Gonadotropins-Induced Meiotic Maturation of Porcine Oocytes.Biol Reprod.2015 Dec;93(6):131.
• [13] 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.