Details of the Drug Combination

General Information of Drug Combination (ID: DC7K8QS)

• Drug Combination Name: Cinacalcet + Pepstatin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Cinacalcet (DMCX0K3): Small molecular drug
  Pepstatin (DM9S1EA): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 16.99
  Bliss Independence Score: 16.99
  Loewe Additivity Score: 28.57
  LHighest Single Agent (HSA) Score: 28.57

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	[4]

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	[5]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[5]

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	[7]
Parathyroid hormone (PTH)	OTD721UF	PTHY_HUMAN	Decreases Expression	[8]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[9]

Indication(s) of Pepstatin

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Terminated	[3]

Pepstatin Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium Cysteine protease falcipain-2 (Malaria CPF2)	TT7EASG	Q9N6S8_PLAFA	Inhibitor	[10]
Plasmodium Plasmepsin 2 (Malaria PLA2)	TTXMNHO	PLM2_PLAFA	Inhibitor	[11]
Plasmodium Plasmepsin 1 (Malaria PLA1)	TTH9VL3	PLM1_PLAFA	Inhibitor	[11]
Plasmodium Cysteine protease falcipain (Malaria CPF)	TTJNPTK	NOUNIPROTAC	Inhibitor	[11]

Pepstatin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cathepsin D (CTSD)	OTQZ36F3	CATD_HUMAN	Decreases Activity	[12]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [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] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004280)
• [4] Clinical pipeline report, company report or official report of Amgen (2009).
• [5] Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11.
• [6] Effects of CYP3A inhibition on the metabolism of cilostazol. Clin Pharmacokinet. 1999;37 Suppl 2:61-8.
• [7] Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. Eur J Clin Pharmacol. 2007 Feb;63(2):159-63.
• [8] 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.
• [9] 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.
• [10] Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97.
• [11] Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
• [12] Evidence of a lysosomal pathway for apoptosis induced by the synthetic retinoid CD437 in human leukemia HL-60 cells. Cell Death Differ. 2001 May;8(5):477-85. doi: 10.1038/sj.cdd.4400843.