Details of the Drug Combination

General Information of Drug Combination (ID: DCQ7FUV)

• Drug Combination Name: Cinacalcet + Eplerenone
• Indication: Primary Hyperparathyroidism; Status: Phase 2 [1]
• Component Drugs:
  Cinacalcet (DMCX0K3): Small molecular drug
  Eplerenone (DMF0NQR): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cinacalcet

Disease Entry	ICD 11	Status	REF
Hyperparathyroidism	5A51	Approved	[2]
Kidney disease	GC2Z	Phase 3	[2]

Cinacalcet Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Extracellular calcium-sensing receptor (CASR)	TTBUYHA	CASR_HUMAN	Agonist	[5]

Cinacalcet Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[6]

Cinacalcet Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[8]
Parathyroid hormone (PTH)	OTD721UF	PTHY_HUMAN	Decreases Expression	[9]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[10]

Indication(s) of Eplerenone

Disease Entry	ICD 11	Status	REF
Heart failure	BD10-BD13	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[4]

Eplerenone Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HUMAN mineralocorticoid receptor (MR)	TT9P1CK	MCR_HUMAN	Antagonist	[4]
Mineralocorticoid receptor (MR)	TT26PHO	MCR_HUMAN	Modulator	[11]

Eplerenone Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[13]

Eplerenone Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Abundance	[13]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Abundance	[13]

References

• [1] ClinicalTrials.gov (NCT02525796) Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism
• [2] 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: 3308).
• [3] 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: 2876).
• [4] Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020 Mar 16;6:14.
• [5] Clinical pipeline report, company report or official report of Amgen (2009).
• [6] Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11.
• [7] Effects of CYP3A inhibition on the metabolism of cilostazol. Clin Pharmacokinet. 1999;37 Suppl 2:61-8.
• [8] Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. Eur J Clin Pharmacol. 2007 Feb;63(2):159-63.
• [9] Normalization of lithium-induced hypercalcemia and hyperparathyroidism with cinacalcet hydrochloride. Am J Kidney Dis. 2006 Nov;48(5):832-7. doi: 10.1053/j.ajkd.2006.07.019.
• [10] Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [12] Eplerenone: a selective aldosterone receptor antagonist for hypertension and heart failure. Heart Dis. 2003 Sep-Oct;5(5):354-63.
• [13] The relative role of CYP3A4 and CYP3A5 in eplerenone metabolism. Toxicol Lett. 2019 Oct 15;315:9-13.