Details of the Drug

General Information of Drug (ID: DM10ZJP)

• Drug Name: Ronacaleret
• Synonyms: Ronacaleret; UNII-DIH95YP7J3; DIH95YP7J3; CHEMBL1198855; 753449-67-1; SB-751689; Ronacaleret [INN]; SCHEMBL3737849; GTPL9473; BDBM50346036; AKOS030261487; DB05255; SB16763; SB 751689; 3-[3-[(2R)-3-[[1-(2,3-dihydro-1H-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4,5-difluorophenyl]propanoic acid; 3-[3-[[(2R)-3-[[2-(2,3-Dihydro-1H-indene-2-yl)-1,1-dimethylethyl]amino]-2-hydroxypropyl]oxy]-4,5-difluorophenyl]propionic acid

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 447.5
  Topological Polar Surface Area (xlogp); 1.7
  Rotatable Bond Count (rotbonds); 11
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C25H31F2NO4
  IUPAC Name: 3-[3-[(2R)-3-[[1-(2,3-dihydro-1H-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]-4,5-difluorophenyl]propanoic acid
  Canonical SMILES: CC(C)(CC1CC2=CC=CC=C2C1)NC[C@H](COC3=C(C(=CC(=C3)CCC(=O)O)F)F)O
  InChI: InChI=1S/C25H31F2NO4/c1-25(2,13-17-9-18-5-3-4-6-19(18)10-17)28-14-20(29)15-32-22-12-16(7-8-23(30)31)11-21(26)24(22)27/h3-6,11-12,17,20,28-29H,7-10,13-15H2,1-2H3,(H,30,31)/t20-/m1/s1
  InChIKey: FQJISUPNMFRIFZ-HXUWFJFHSA-N
• Cross-matching ID:
  PubChem CID: 10345214
  CAS Number: 753449-67-1
  DrugBank ID: DB05255
  TTD ID: D07XPT
  VARIDT ID: DR00729

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	[2]

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] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023902)
• [2] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [3] Clinical pipeline report, company report or official report of Amgen (2009).
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035616)
• [6] Antagonist for calcium-sensing receptor. JTT-305/MK-5442. Clin Calcium. 2011 Jan;21(1):89-93.
• [7] 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.
• [8] 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.
• [9] Mixed-effects modeling of the pharmacodynamic response to the calcimimetic agent R-568. Clin Pharmacol Ther. 1999 Jan;65(1):40-9.
• [10] 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.
• [11] The Extracellular Calcium-Sensing Receptor (CASR) Regulates Gonadotropins-Induced Meiotic Maturation of Porcine Oocytes.Biol Reprod.2015 Dec;93(6):131.
• [12] 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.