Details of the Drug Combination

General Information of Drug Combination (ID: DCCTI79)

• Drug Combination Name: Pargyline + Nitisinone
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Pargyline (DMM0HR1): Small molecular drug
  Nitisinone (DMVS9WQ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 0.61
  Bliss Independence Score: 0.61
  Loewe Additivity Score: 14.06
  LHighest Single Agent (HSA) Score: 14.06

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pargyline

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[2]
Muscular dystrophy	8C70	Patented	[3]
Skin imperfections	EK71	Patented	[3]

Pargyline Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Monoamine oxidase (MAO)	TT32XQJ	NOUNIPROTAC	Inhibitor	[3]
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[5]

Pargyline Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Decreases Activity	[6]
Amine oxidase B (MAOB)	OTTDFM1O	AOFB_HUMAN	Decreases Activity	[7]

Indication(s) of Nitisinone

Disease Entry	ICD 11	Status	REF
Hereditary tyrosinemia type 1	5C50.11	Approved	[4]

Nitisinone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Hydroxyphenylpyruvate dioxygenase (HPD)	TT8DSFC	HPPD_HUMAN	Inhibitor	[8]

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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Novel monoamine oxidase inhibitors: a patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):91-110.
• [4] 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: 6834).
• [5] Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H821-8.
• [6] Evaluation of metabolism dependent inhibition of CYP2B6 mediated bupropion hydroxylation in human liver microsomes by monoamine oxidase inhibitors and prediction of potential as perpetrators of drug interaction. Chem Biol Interact. 2015 Mar 25;230:9-20.
• [7] Combining initro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. Chem Biol Interact. 2016 Jul 25;254:135-45.
• [8] Experience of nitisinone for the pharmacological treatment of hereditary tyrosinaemia type 1. Expert Opin Pharmacother. 2008 May;9(7):1229-36.