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

General Information of Drug (ID: DMJXZD5)

• Drug Name: calhex 231 Drug Info
• Synonyms: calhex-231

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 11849514
  TTD Drug ID: DMJXZD5

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cinacalcet	DMCX0K3	Hyperparathyroidism	5A51	Approved	[3]
Etelcalcetide	DMHP9BL	Secondary hyperparathyroidism	5A51.1	Approved	[4]
ASP7991	DM3TN1A	Hyperparathyroidism	5A51	Phase 2	[5]
MK-5442	DMHTIGU	Osteoporosis	FB83.0	Phase 2	[6]
ATF-936	DMWGKHZ	Osteoporosis	FB83.0	Phase 1	[7]
AXT-914	DM7ZU3B	Osteoporosis	FB83.0	Phase 1	[8]
R-568	DM5NWPD	N. A.	N. A.	Discontinued in Phase 2	[9]
Ronacaleret	DM10ZJP	Osteoporosis	FB83.0	Discontinued in Phase 2	[10]
NPS-2143	DMQPXLF	Osteoporosis	FB83.0	Discontinued in Phase 2	[11]
NPS-2390	DMMRY0Z	Cerebrovascular ischaemia	8B1Z	Preclinical	[12]

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 (allosteric modulator)	[2]

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: 714).
• [2] Modeling and mutagenesis of the binding site of Calhex 231, a novel negative allosteric modulator of the extracellular Ca(2+)-sensing receptor. J Biol Chem. 2003 Dec 5;278(49):49487-94.
• [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] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [11] 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.
• [12] The Extracellular Calcium-Sensing Receptor (CASR) Regulates Gonadotropins-Induced Meiotic Maturation of Porcine Oocytes.Biol Reprod.2015 Dec;93(6):131.